ELECTIVE DOUBLE EUPLOID EMBRYO TRANSFER IN ADVANCED MATERNAL AGE COUPLES – IS THERE A BENEFICIAL ROLE?

Abstract Study question Can PGT-A reduce the anxiety generally experienced by infertile women undergoing IVF in the waiting period between embryo transfer and the pregnancy test? Summary answer PGT-A reduces anxiety in infertile women after embryo transfer, probably due to a gain of confidence in their treatment route. What is known already The waiting period, i.e. the time between embryo-transfer and the pregnancy-test, is considered unpredictable and unmanageable, thus figuring amongst the most stressful steps of an IVF treatment. This is mainly imputable to women’s lost sense of control over the outcome. Uncertainty is in fact a source of fear and elevated distress. PGT-A has been shown to improve live birth rate per embryo transfer and reduce miscarriage rate per clinical pregnancy across several trials and observational studies worldwide, especially in advanced maternal age (AMA) women. Here, we investigated if euploid embryo transfer does involve also lower emotional burden over untested one. Study design, size, duration Prospective observational study evaluating the level of anxiety in the waiting period among women undergoing euploid or untested embryo transfer. Data were collected between September 2019 and September 2020 in a public hospital. A total of 48 infertile women were recruited: 25 undergoing euploid single embryo transfer after trophectoderm biopsy and NGS, and 23 undergoing untested single embryo transfer. Participants/materials, setting, methods To measure the level of anxiety, the two groups completed the STAI (State Trait Anxiety Inventory) questionnaire at two time points: before starting the ovarian stimulation (T0), and at day 8 after embryo transfer (T1). The chosen questionnaire has been previously validated to capture the level of patients’ anxiety during the waiting period. Outcomes of T0 were used to control for individual level state of anxiety at T1. Main results and the role of chance The two groups showed similar reproductive history and sociodemographic characteristics except for female age, which was higher in the PGT-A group (37.7±3.2 yr versus 32.3±2.2 yr in the control). This is due to AMA (maternal age >35 yr) being the main indication to PGT-A. Conversely, the duration of infertility was similar in the two groups (3.8±2.2 yr versus 3.7±1.9 in the control). At T0 all patients showed similar levels of anxiety (46.4 points versus 49.9 in the control, 95%CI of the difference: from –9.97 to 3.03 points, p = 0.3). Remarkably, at T1 instead, the women undergoing euploid embryo transfer showed a significantly decreased level of anxiety with respect to the control (39.9 points versus 53.4; 95% CI of the difference: from –18.26 to –8.69, p < 0.01). This difference remained significant also after controlling for the baseline value at T0, and adjusting for potential confounding factors in a multivariate analysis (adjusted p-value<0.01). Limitations, reasons for caution The sample size is small, yet the study resulted powered enough to reveal the considerable advantage of PGT-A toward the primary outcome. We analysed only the waiting period here. Therefore, data will be collected in the future at subsequent gestational stages, such as when prenatal genetic diagnosis is usually conducted. Wider implications of the findings: Women undergoing PGT-A seem reassured by the technique. This is probably due to the gain of confidence and control derived from an increased expectation of success. From this perspective, assessing women’s wellbeing and attitude towards all different clinical procedures should become a critical part of their treatment. Trial registration number None

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Perinatal and maternal outcomes after frozen versus fresh embryo transfer cycles in women of advanced maternal age

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/j.ejogrb.2020.09.047 ◽

2020 ◽

Author(s):

Xinyi Zhang ◽

Lina Bai ◽

Haiqin Ren ◽

Xinyu Liu ◽

Shuaishuai Guo ◽

...

Keyword(s):

Embryo Transfer ◽

Maternal Age ◽

Advanced Maternal Age ◽

Maternal Outcomes ◽

Fresh Embryo Transfer

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PERINATAL AND MATERNAL OUTCOMES AFTER FROZEN VERSUS FRESH EMBRYO TRANSFER CYCLES IN WOMEN OF ADVANCED MATERNAL AGE

Fertility and Sterility ◽

10.1016/j.fertnstert.2020.08.852 ◽

2020 ◽

Vol 114 (3) ◽

pp. e313

Author(s):

Xinyi Zhang ◽

Jichun Tan

Keyword(s):

Embryo Transfer ◽

Maternal Age ◽

Advanced Maternal Age ◽

Maternal Outcomes ◽

Fresh Embryo Transfer

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Reduction of multiple pregnancies in the advanced maternal age population after implementation of an elective single embryo transfer policy coupled with enhanced embryo selection: pre- and post-intervention study

Human Reproduction ◽

10.1093/humrep/dev159 ◽

2015 ◽

Vol 30 (9) ◽

pp. 2097-2106 ◽

Cited By ~ 68

Author(s):

Filippo Maria Ubaldi ◽

Antonio Capalbo ◽

Silvia Colamaria ◽

Susanna Ferrero ◽

Roberta Maggiulli ◽

...

Keyword(s):

Embryo Transfer ◽

Maternal Age ◽

Intervention Study ◽

Advanced Maternal Age ◽

Single Embryo Transfer ◽

Embryo Selection ◽

Multiple Pregnancies ◽

Post Intervention ◽

Transfer Policy ◽

Elective Single Embryo Transfer

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Ideal Stage of Embryo Transfer to Improve Outcomes for Women of Advanced Maternal Age

10.21203/rs.3.rs-847328/v1 ◽

2021 ◽

Author(s):

Xue Wang ◽

Yaling Xiao ◽

Zhengyi Sun ◽

Jingran Zhen ◽

Qi Yu

Keyword(s):

Embryo Transfer ◽

Maternal Age ◽

Formation Rate ◽

Live Birth Rate ◽

Advanced Maternal Age ◽

Blastocyst Transfer ◽

Fresh Embryo Transfer ◽

Advantages And Disadvantages ◽

Cancellation Rate ◽

Freezing Cycle

Abstract Background The purpose of this retrospective study was to optimise the transplantation strategy for women of advanced maternal age to achieve live births within the shortest time. Methods Data were collected from patients older than 40 years who underwent assisted reproductive therapy at our centre from 1 January 2009 to 31 December 2019. A total of 1233 cases of fresh cleavage embryo transfer cycles, 280 cases of frozen-thawed blastocyst transfer cycles, and 26 cases of frozen-thawed cleavage embryo transfer cycles were included. Multivariable logistic regression was performed to adjust for confounding factors. Results The main outcome was the live birth rate. The secondary outcomes were the clinical pregnancy rate, spontaneous abortion rate, and neonatal outcomes. We found that the blastocyst formation rate of patients older than 40 years was 23.5%, the freezing cycle rate was 19.8%, and the fresh embryo transfer rate was 83.0%. Conclusions Cleavage embryo transfer should be performed first to reduce the cycle cancellation rate. If the number of retrieved oocytes is more than eight, then blastocyst transplantation can be considered after fully discussing the advantages and disadvantages of blastocyst culture with patients. Alternatively, cleavage embryo transfer can be performed first, and frozen-thawed blastocyst transfer can be performed next if cleavage embryo transfer is unsuccessful.

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P–415 Clinical and In Vitro Fertilization laboratory parameters that contribute to clinical miscarriage after single euploid embryo transfer

Human Reproduction ◽

10.1093/humrep/deab130.414 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

M D C Nogale. Barrios ◽

J A García-Velasco ◽

M Cruz ◽

S D Frutos ◽

E M Martínez ◽

...

Keyword(s):

Embryo Transfer ◽

Maternal Age ◽

Pregnancy Loss ◽

Endometrial Thickness ◽

Miscarriage Rate ◽

Vitro Fertilization ◽

Endometrial Preparation ◽

Euploid Embryo

Abstract Study question To investigate which factors, excluding embryo aneuploidies, are associated with miscarriage in patients who have undergone a single euploid blastocyst transfer. Summary answer Miscarriage was related to the body mass index (BMI), the type of cycle and the thickness of the endometrium. What is known already Preimplantation genetic testing for aneuploidies (PGT-A) is widely used in-vitro fertilization (IVF) to select euploid embryos. Several studies have shown that embryo aneuploidy is the main contributing factor for IVF failure, reinforcing the relevance of PGT-A as a method to select chromosomally normal embryos. A recent meta-analysis confirmed that patients undergoing PGT-A have a lower miscarriage rate than women that conceived naturally (9% vs 28%, respectively). Even though most of the studies show that PGT-A significantly reduces miscarriage rate, still some women do lose their pregnancies. We investigated which other reasons may be related to this early pregnancy loss. Study design, size, duration Retrospective, observational, and multicenter study of 6910 patients undergoing single euploid blastocyst transfer after PGT-A from January 2017 to December 2019 in our institution. Several laboratory and clinic variables were analyzed to study the effect of these variables on the miscarriage rate Participants/materials, setting, methods Indications for PGT-A were advanced maternal age, implantation failure, recurrent pregnancy loss and male factor. Embryos were cultured 5% O2 concentration and 6.5% CO2 concentration. Trophectoderm biopsy was performed on day 5/6 of development and analyzed through Next Generation Sequencing (NGS); embryos were vitrified until transfer was performed. Single euploid embryo transfer was performed in all cases. We performed a multivariate regression analysis to compare the different variables and search for there are significant differences. Main results and the role of chance We studied a total of 6910 patients undergoing PGT-A to describe which factors, excluding embryo aneuploidies, were correlated with miscarriage in patients who underwent single thawed euploid embryo transfer. When considering embryo morphology (embryo grading, quality of inner cell and quality of trophectoderm), we did not find differences in miscarriage rate among groups (high quality= 15.9%; normal quality= 14.3%; low quality= 15.0%; poor quality= 14.8%) p = 0.833. BMI was significantly associated with miscarriage rate (odds ratio [OD] 1.04; 95% confidence interval [CI], 1.012–1–076 p = 0.006) and miscarriage rate. We observed a weak association between endometrial thickness and miscarriage rate ([OD] 0.65; 95%, 0.528–0.778 p = 0.04) and also between type of endometrial preparation (natural cycle or hormone replacement cycle) ([OD] 0.77; 95%, 0.528–0.778) p = 0.04. Body mass index, according to our findings, was the main variable correlated with miscarriage rate. We did not find any association with the other variables studied (biopsy day, maternal age, male age, duration infertility, cycle length, previous miscarriage, previous live birth, previous cycles IVF, endometrial pattern and diagnosis). Limitations, reasons for caution The retrospective study design limits the generalization of our results but offers a good insight to be validated in prospective trials. Wider implications of the findings: According to our findings, BMI, endometrial thickness the day of the embryo transfer, and the type of endometrial preparation should be considered when transferring an euploid blastocyst. Trial registration number NO APLICA

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P–390 The intrauterus administration of peripheral blood mononuclear cells increase the pregnancy rates for the patients with advanced maternal age after single euploid embryo transfer

Human Reproduction ◽

10.1093/humrep/deab130.389 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

E Zhylkova ◽

O Feskov ◽

V Feskov ◽

O Somova ◽

Y Zin ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Maternal Age ◽

Mononuclear Cells ◽

Advanced Maternal Age ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Implantation Rates ◽

Group 2 ◽

Euploid Embryo

Abstract Study question Does the intrauterine administration of peripheral blood mononuclear cells (PBMCs) effect the outcome of IVF for patients with advanced maternal age when the euploid embryos after PGT-A are transferred? Summary answer The implantation rates were significantly higher after the intrauterine application of PBMCs in patients with advanced maternal age (AMA) before transfer of the euploid embryo. What is known already The aneuploidy rates of blastocysts in IVF is in range 45–70% depending on different factors. Besides that, the endometrium plays an important role in achieving optimal outcomes of assisted reproductive technologies. It has been proposed that intrauterine administration of peripheral blood mononuclear cells modulates maternal immune response to favor implantation. Study design, size, duration The effect of the intrauterine application of PBMCs to improve the implantation rates in the group of patients with advanced maternal age was studied. Two group of patients (PBMCs-group and non-PBMCs-group_ were formed. Single euploid embryo was transferred for each patient. Participants/materials, setting, methods: The ploidy status of 373 blastocysts from 82 AMA-patients was analyzed by the method of next generation sequencing (NGS). PBMCs were applied for 39 women with the mean age 39.2±3.2 y.o. before embryo transfer (Group 1). For 43 patients with the mean age 38.2±2.1 y.o. single euploid embryo transfers were performed without PBMCs administration (Group 2). Chi-squared test was used for data analysis. The study’s protocol was approved by the Center’s IRB. Main results and the role of chance Totally the rate of euploid embryos was 27.1% (101 blastocysts). In the mentioned study 55.0% of examined blastocysts were aneuploid (205 embryos) and 17.9% of blastocysts were detected as mosaic (67 embryos). Single euploid embryo was transferred in each case in the patients of both experimental groups. The implantation rate was significantly higher in Group 1 with PBMCs application comparing with non-PBMCs experimental Group 2 (38.5% (15 pregnancies) vs. 23.3% (10 pregnancies), df = 1, χ2 = 5.487, χ2critical = 3.841, P = 0.020). Limitations, reasons for caution The embryo biopsy was performed only for blastocyst with top-quality morphology. Wider implications of the findings: The implantation rates were significantly higher when the intrauterine application of PBMCs in patients with advanced maternal age before the transfer of the euploid embryo (P = 0.020). The randomized studies to improve our knowledge in immunogenic therapy in reproductive medicine should be performed. Trial registration number -

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Day 3 Versus Day 5 Embryo Transfer in Women of Advanced Maternal Age

Fertility and Sterility ◽

10.1016/j.fertnstert.2010.01.085 ◽

2010 ◽

Vol 93 (5) ◽

pp. S10-S10

Author(s):

W. Chang ◽

C. Briton-Jones ◽

N. Buehler ◽

H. Danzer ◽

M. Surrey ◽

...

Keyword(s):

Embryo Transfer ◽

Maternal Age ◽

Advanced Maternal Age

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

Reproductive Sciences ◽

10.1177/1933719118799192 ◽

2018 ◽

Vol 26 (6) ◽

pp. 806-811 ◽

Cited By ~ 1

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.

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