囊胚形態  正確生長天數速度  是影響囊胚冷凍存活率&著床最重要指標

Hum Reprod. 2018 Nov 1;33(11):1992-2001. doi: 10.1093/humrep/dey291.

Associations of blastocyst features, trophectoderm biopsy and other laboratory practice with post-warming behavior and implantation.

Cimadomo D1, Capalbo A2,3, Levi-Setti PE4, Soscia D1, Orlando G1, Albani E4, Parini V4, Stoppa M1, Dovere L1, Tacconi L1, Ievoli E1, Maggiulli R1, Ubaldi FM1, Rienzi L1.

Author information

Abstract

STUDY QUESTION:

Are trophectoderm biopsy or other pre-vitrification features or laboratory practices associated with differences in blastocyst post-warming behavior (degeneration, re-expansion and live birth after single embryo transfer (SET))?

SUMMARY ANSWER:

Blastocyst morphology, day of full development and artificial shrinkage (either laser-assisted or biopsy-induced) are the pre-vitrification parameters/practices most strongly associated with post-warming behavior and implantation potential while there was no association with trophectoderm biopsy.

WHAT IS KNOWN ALREADY:

Since the introduction of vitrification, the adoption of cycle segmentation, freeze-all and SET policies, as well of trophectoderm biopsy-based aneuploidy testing (i.e. pre-implantation genetic testing for aneuploidies (PGT-A)), the number of blastocysts vitrified worldwide has increased greatly. Previous studies already defined generally high blastocyst cryo-survival rates after vitrification-warming (>95%), along with a positive correlation between blastocyst re-expansion and morphology with implantation. Additionally, artificial shrinkage has been outlined as a potentially beneficial procedure, while the association between embryo cryo-survival and trophectoderm biopsy is still unclear.

STUDY DESIGN, SIZE, DURATION:

Cohort study conducted at two IVF centers (1 and 2). A total of 2129 consecutive SETs using vitrified-warmed blastocysts in either non-PGT or PGT-A cycles between June 2016 and August 2017 were included. A freeze-all strategy was in place and three main pre-vitrification practices were used: (i) no biopsy and no artificial shrinkage (Clinic 1); (ii) trophectoderm biopsy and vitrification of collapsed blastocyst within 30 min (Clinics 1 and 2); and (iii) no biopsy but laser-assisted artificial shrinkage (Clinic 2). The primary outcome was the blastocyst degeneration rate. Overall, 2108 surviving blastocysts were graded at 1.5 h after warming for degeneration (absent or partial) and re-expansion (full, partial or absent) grades and post-warming morphological quality. Logistic regression analyses were conducted to assess the association of any pre-vitrification feature with blastocyst post-warming behavior. The logistic regressions conducted upon live birth after either untested or euploid SET also included the post-warming characteristics.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Center 1 is a private IVF facility, while center 2 is the IVF facility of a University hospital. In non-PGT cycles, ICSI with blastocyst culture up to full-expansion and vitrification were performed. At center 1 the untested blastocysts were vitrified when still expanded, while at center 2 they underwent laser-assisted artificial shrinkage. In PGT-A cycles, in both clinics, trophectoderm biopsy (which involves laser-assisted shrinkage) was done without previous zona-opening on Day 3, and vitrification was performed within 30 min whilst the blastocyst remained collapsed. A qPCR-based chromosome analysis was conducted. Only SETs were performed (euploid-SET in case of PGT-A). Any cycle-, laboratory- and embryo-based feature which could impact blastocyst post-warming behavior was included in the analyses as putative confounder.

MAIN RESULTS AND THE ROLE OF CHANCE:

The overall degeneration rate was 1% (N = 21/2129). The results were consistent among different vitrification/warming operators or kits used, as well as any other IVF laboratory-related parameter. Blastocyst artificial shrinkage (either laser-assisted or biopsy-induced) involved a lower risk of degeneration after warming (odds ratio (OR) [95% CI] = 0.26 [0.09-0.79]). Conversely, both poor morphological quality pre-vitrification and taking 7 days to reach full blastulation resulted in a significantly higher risk (OR [95% CI] = 11.67 [3.42-39.83] and 4.43 [1.10-20.55], respectively). Importantly, trophectoderm biopsy did not show any association with blastocyst cryo-survival/degeneration. Overall 2.5% (N = 53/2108) blastocysts failed to re-expand post-warming. The only parameters significantly associated with no blastocyst re-expansion post-warming were average (OR [95% CI] = 4.96 [2.20-11.21]) or poor (OR [95% CI] = 19.54 [8.39-45.50]) morphological quality and taking 7 days to reach full blastulation (OR [95% CI] = 3.19 [1.23-8.29]), as well as prevention of spontaneous hatching pre-vitrification (OR [95% CI] = 0.10 [0.01-0.85]). The post-warming features of the survived blastocyst (i.e. degeneration and re-expansion scores and morphological quality) showed no significant association with vitrified blastocyst competence (i.e. live birth) when corrected for pre-vitrification ones (i.e. morphological quality, day of full development and, for untested SET, maternal age at oocyte retrieval). Of note, poor-quality blastocysts pre-vitrification showed a high overall cryo-survival rate post-warming 92.8% (N = 116/125), but the live birth rates were only 2.1% (N = 1/48) and 7.3% (N = 5/68) after untested and euploid SET, respectively.

精蟲品質差之病患  形成囊胚染色體異常率較高

J Assist Reprod Genet. 2020 Jan 4. doi: 10.1007/s10815-019-01673-w. [Epub ahead of print]

High rates of aneuploidy, mosaicism and abnormal morphokinetic development in cases with low sperm concentration.

PURPOSE:

The aim of our study was to evaluate the impact of severe male infertility (SMF) on the chromosomal status of embryos and any possible correlation between chromosomal status and embryo morphokinetics in younger women using data obtained from comprehensive preimplantation genetic tests.

METHODS:

The trial was conducted in an ART and Reproductive Genetics Centre between 2011 and 2018. A total of 326 cycles in cases with SMF where the female partner's age was ≤ 35 years were evaluated. SMF is defined as sperm concentration below 5 mil/ml (million per milliliter) and divided into three subgroups according to sperm concentrations: 1-5 mil/ml, < 1mil/ml and testicular sperm. The control group of 190 cycles had normal sperm parameters.

RESULTS:

Significantly lower chromosomal euploidy rates were found in the testicular sperm group compared with the normal sperm controls when the female age was ≤ 35 years. In SMF, statistically significantly affected chromosomes were 2, 10, 11, 17, 21 and sex chromosomes. The mosaicism and abnormal morphokinetic development rates were higher in the SMF group than in control group, and this difference was significant when testicular sperm was used.

CONCLUSION:

Lower euploidy rates, higher mosaicism rates and a higher incidence of abnormal morphokinetic development were observed in cases with testicular sperm with female partners ≤ 35 years compared with normal sperm controls. These findings suggest that PGT-A may be advisable in severe male infertility cases. Furthermore, the correlation between morphokinetics and chromosomal status was greatly reduced or absent in these most severe forms of male infertility, thus the need for new morphokinetic models.

除非PCO，一般病患採用全部凍胚並無法提高懷孕率

N Engl J Med. 2018 Jan 11;378(2):137-147. doi: 10.1056/NEJMoa1703768.

IVF Transfer of Fresh or Frozen Embryos in Women without Polycystic Ovaries.

Vuong LN1, Dang VQ1, Ho TM1, Huynh BG1, Ha DT1, Pham TD1, Nguyen LK1, Norman RJ1, Mol BW1.

Author information

Abstract

BACKGROUND:

Among women who are undergoing in vitro fertilization (IVF), the transfer of frozen embryos has been shown to result in a higher rate of live birth than the transfer of fresh embryos in those with infertility associated with the polycystic ovary syndrome. It is not known whether frozen-embryo transfer results in similar benefit in women with infertility that is not associated with the polycystic ovary syndrome.

METHODS:

We randomly assigned 782 infertile women without the polycystic ovary syndrome who were undergoing a first or second IVF cycle to receive either a frozen embryo or a fresh embryo on day 3. In the frozen-embryo group, all grade 1 and 2 embryos had been cryopreserved, and a maximum of two embryos were thawed on the day of transfer in the following cycle. In the fresh-embryo group, a maximum of two fresh embryos were transferred in the stimulated cycle. The primary outcome was ongoing pregnancy after the first embryo transfer.

RESULTS:

After the first completed cycle, ongoing pregnancy occurred in 142 of 391 women (36.3%) in the frozen-embryo group and in 135 of 391 (34.5%) in the fresh-embryo group (risk ratio in the frozen-embryo group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P=0.65). Rates of live birth after the first transfer were 33.8% and 31.5%, respectively (risk ratio, 1.07; 95% CI, 0.88 to 1.31).

CONCLUSIONS:

Among infertile women without the polycystic ovary syndrome who were undergoing IVF, the transfer of frozen embryos did not result in significantly higher rates of ongoing pregnancy or live birth than the transfer of fresh embryos. (Funded by My Duc Hospital; ClinicalTrials.gov number, NCT02471573 .).

桑葚化 (TM, Time of morulation)<80H+優質Trophectoderm(TE) vs TM>80h+差質TE
----活產率 55% vs 25%

Fertil Steril. 2019 Dec;112(6):1080-1093.e1. doi: 10.1016/j.fertnstert.2019.07.1322.

Time of morulation and trophectoderm quality are predictors of a live birth after euploid blastocyst transfer: a multicenter study.

Rienzi L1, Cimadomo D2, Delgado A3, Minasi MG4, Fabozzi G2, Gallego RD3, Stoppa M2, Bellver J3, Giancani A5, Esbert M6, Capalbo A7, Remohì J3, Greco E4, Ubaldi FM2, Meseguer M3.

Author information

Abstract

OBJECTIVE:

To investigate whether the morphodynamic characterization of a euploid blastocyst's development allows a higher prediction of a live birth after single-embryo-transfer (SET).

DESIGN:

Observational cohort study conducted in two phases: training and validation.

SETTING:

Private in vitro fertilization centers.

PATIENT(S):

Euploid blastocysts: 511 and 319 first vitrified-warmed SETs from 868 and 546 patients undergoing preimplantation genetic testing for aneuploidies (PGT-A) in the training and validation phase, respectively.

INTERVENTION(S):

Data collected from time of polar body extrusion to time of starting blastulation, and trophectoderm and inner-cell-mass static morphology in all embryos cultured in a specific time-lapse incubator with a continuous medium. Logistic regressions conducted to outline the variables showing a statistically significant association with live birth. In the validation phase, these variables were tested in an independent data set.

MAIN OUTCOME MEASURE(S):

Live births per SET.

RESULT(S):

The average live birth rate (LBR) in the training set was 40% (N = 207/511). Only time of morulation (tM) and trophectoderm quality were outlined as putative predictors of live birth at two IVF centers. In the validation set, the euploid blastocysts characterized by tM <80 hours and high-quality trophectoderm resulted in a LBR of 55.2% (n = 37/67), while those with tM ≥ 80 hours and a low-quality trophectoderm resulted in a LBR of 25.5% (N = 13/51).

CONCLUSION(S):

Time of morulation and trophectoderm quality are better predictors of a euploid blastocyst's reproductive competence. Our evidence was reproducible across different centers under specific culture conditions. These data support the crucial role of morulation for embryo development, a stage that involves massive morphologic, cellular, and molecular changes and deserves more investigation.

PCO病患合併過度肥胖 BMI越高 (BMI ≥ 30 kg/m2)  流產率越高

Fertil Steril. 2019 Dec;112(6):1172-1179. doi: 10.1016/j.fertnstert.2019.08.009.

Effect of body mass index on pregnancy outcomes with the freeze-all strategy in women with polycystic ovarian syndrome.

Abstract

OBJECTIVE:

To investigate the effects of body mass index (BMI) on assisted reproductive outcomes with the freeze-all strategy for patients with polycystic ovary syndrome (PCOS).

DESIGN:

Retrospective cohort study.

SETTING:

Tertiary care academic medical center.

PATIENT(S):

A total of 3,079 women with PCOS across different BMIs at our institution from January 2015 to May 2017 were stratified into cohorts.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Implantation rate, clinical pregnancy rate, early miscarriage rate, and live birth rate.

RESULT(S):

The live birth rate was most favorable in underweight (BMI < 18.5 kg/m2) and normal weight cohorts (18.5 ≤ BMI < 25 kg/m2) and progressively decreased as BMI increased. Moreover, the obese cohort (BMI ≥ 30 kg/m2) of patients with PCOS who had frozen ET cycles had a relatively high early miscarriage rate.

CONCLUSION(S):

The live birth rates are highest in underweight and normal weight patients with PCOS undergoing IVF with the freeze-all strategy. Furthermore, there is a progressive and statistically significant decrease in the live birth rate and an increase in the miscarriage rate in obese patients with PCOS.

PGD僅小幅度改善反覆性流產病患之活產率 (26.8 versus 21.1%，統計無明顯差異)

Hum Reprod. 2019 Dec 1;34(12):2340-2348. doi: 10.1093/humrep/dez229.

Preimplantation genetic testing for aneuploidy: a comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure.

Abstract

STUDY QUESTION:

Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate and reduce the miscarriage rate in patients with recurrent pregnancy loss (RPL) caused by an abnormal embryonic karyotype and recurrent implantation failure (RIF)?

SUMMARY ANSWER:

PGT-A could not improve the live births per patient nor reduce the rate of miscarriage, in both groups.

WHAT IS KNOWN ALREADY:

PGT-A use has steadily increased worldwide. However, only a few limited studies have shown that it improves the live birth rate in selected populations in that the prognosis has been good. Such studies have excluded patients with RPL and RIF. In addition, several studies have failed to demonstrate any benefit at all. PGT-A was reported to be without advantage in patients with unexplained RPL whose embryonic karyotype had not been analysed. The efficacy of PGT-A should be examined by focusing on patients whose previous products of conception (POC) have been aneuploid, because the frequencies of abnormal and normal embryonic karyotypes have been reported as 40-50% and 5-25% in patients with RPL, respectively.

STUDY DESIGN, SIZE, DURATION:

A multi-centre, prospective pilot study was conducted from January 2017 to June 2018. A total of 171 patients were recruited for the study: an RPL group, including 41 and 38 patients treated respectively with and without PGT-A, and an RIF group, including 42 and 50 patients treated respectively with and without PGT-A. At least 10 women in each age group (35-36, 37-38, 39-40 or 41-42 years) were selected for PGT-A groups.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

All patients and controls had received IVF-ET for infertility. Patients in the RPL group had had two or more miscarriages, and at least one case of aneuploidy had been ascertained through prior POC testing. No pregnancies had occurred in the RIF group, even after at least three embryo transfers. Trophectoderm biopsy and array comparative genomic hybridisation (aCGH) were used for PGT-A. The live birth rate of PGT-A and non-PGT-A patients was compared after the development of blastocysts from up to two oocyte retrievals and a single blastocyst transfer. The miscarriage rate and the frequency of euploidy, trisomy and monosomy in the blastocysts were noted.

MAIN RESULT AND THE ROLE OF CHANCE:

There were no significant differences in the live birth rates per patient given or not given PGT-A: 26.8 versus 21.1% in the RPL group and 35.7 versus 26.0% in the RIF group, respectively. There were also no differences in the miscarriage rates per clinical pregnancies given or not given PGT-A: 14.3 versus 20.0% in the RPL group and 11.8 versus 0% in the RIF group, respectively. However, PGT-A improved the live birth rate per embryo transfer procedure in both the RPL (52.4 vs 21.6%, adjusted OR 3.89; 95% CI 1.16-13.1) and RIF groups (62.5 vs 31.7%, adjusted OR 3.75; 95% CI 1.28-10.95). Additionally, PGT-A was shown to reduce biochemical pregnancy loss per biochemical pregnancy: 12.5 and 45.0%, adjusted OR 0.14; 95% CI 0.02-0.85 in the RPL group and 10.5 and 40.9%, adjusted OR 0.17; 95% CI 0.03-0.92 in the RIF group. There was no difference in the distribution of genetic abnormalities between RPL and RIF patients, although double trisomy tended to be more frequent in RPL patients.