IVF授精 vs ICSI授精
---IVF造成較高囊胚染色體鑲嵌化  (26 vs 21%)
---IVF造成較高染色體aneuploidy (16.3% vs 9%)

J Assist Reprod Genet. 2019 Jan;36(1):153-157. doi: 10.1007/s10815-018-1347-6. Epub 2018 Oct 25.

Minimizing mosaicism: assessing the impact of fertilization method on rate of mosaicism after next-generation sequencing (NGS) preimplantation genetic testing for aneuploidy (PGT-A).

Palmerola KL1,2, Vitez SF3, Amrane S4,3, Fischer CP5, Forman EJ4.

Abstract

PURPOSE:

Advances in preimplantation genetic testing (PGT) have led to practice changes in assisted reproductive technologies (ART), enabling fertility centers to transfer single embryos while maintaining excellent ongoing pregnancy rates, reducing miscarriage rates, and dramatically reducing ART-associated multiple pregnancies. The introduction of next-generation sequencing (NGS) allows PGT laboratories to assess for embryo mosaicism-although the true incidence and reproductive potential of predicted mosaic embryos are controversial. Due to concern for genetic contamination from other spermatozoa, most reference laboratories require use of intracytoplasmic sperm injection (ICSI) for single gene preimplantation genetic diagnosis (PGT-M). However, in PGT for aneuploidy (PGT-A), conventional insemination (IVF) is typically permissible. The purpose of this study was to evaluate rates of euploid, aneuploid, and mosaic in trophectoderm biopsy samples from embryos in IVF versus ICSI PGT-A cycles. Secondary aims were to assess sex ratio, and subtypes of aneuploidy and mosaicism in IVF versus ICSI PGT-A cycles.

METHODS:

We performed a retrospective review of women undergoing PGT-A at a single academic fertility center from July 1, 2015, to September 1, 2017. In all cycles, PGT-A was performed via trophectoderm biopsy on day 5 or 6 and analyzed using NGS at a single reference lab. We collected and compared patient demographics, fertility testing, cycle characteristics, and PGT-A outcomes between IVF and ICSI cycles.

RESULTS:

Three hundred two PGT-A cycles were included for analysis: 75 IVF and 227 ICSI cycles, resulting in 251 IVF and 724 ICSI biopsied blastocysts. Mean oocyte age of included cycles was 38.6 years (IVF) and 38.5 years (ICSI), p = 0.85. Baseline characteristics of IVF and ICSI PGT-A cycles were similar with the exception of semen parameters: IVF cycles had higher sperm concentration and total motility compared to ICSI cycles. PGT-A outcomes did not differ between IVF and ICSI cycles: euploid 27.9% (IVF) versus 30% (ICSI); aneuploid 45.4% (IVF) versus 43.1% (ICSI); no result 4.4% (IVF) versus 6.2% (ICSI). Though not significant, we identified a trend toward higher rate of mosaicism in IVF (25.9%) versus ICSI (20.9%). Among mosaic embryos, a lower percentage of simple mosaic embryos resulted from IVF (53.8%) versus ICSI (70.2%). Among aneuploid embryos, a non-significant higher percentage of complex aneuploidy resulted from IVF (16.3%) versus ICSI (9%). IVF resulted in a non-significant higher proportion of cycles with no transferrable embryos (42.7%) versus ICSI (36.6%). Numerical and sex chromosome involvement in mosaicism and aneuploidy were similar between IVF and ICSI cycles.

CONCLUSION:

IVF and ICSI NGS PGT-A have similar rates of euploid, aneuploid, and no result embryos, though IVF may result in higher rates of mosaicism and demonstrates differences in proportions of mosaic and aneuploid subtypes compared to ICSI. ICSI may be preferable to conventional insemination to minimize the rate of mosaic results in NGS PGT-A cycles.

A囊胚等級有52%染色體正常
B囊胚等級有42%染色體正常
C囊胚等級有23%染色體正常
D囊胚等級有17%染色體正常

J Assist Reprod Genet. 2019 Aug;36(8):1623-1629. doi: 10.1007/s10815-019-01496-9. Epub 2019 Jun 4.

Euploid blastocysts implant irrespective of their morphology after NGS-(PGT-A) testing in advanced maternal age patients.

Viñals Gonzalez X1, Odia R2, Naja R3, Serhal P4, Saab W4, Seshadri S4, Ben-Nagi J4.

Author information

1

Embryology Department, The Centre For Reproductive and Genetic Health, 230-232 Great Portland St, London, W1W 5QS, UK. xavier.vinalsgonzalez@crgh.co.uk.

2

Embryology Department, The Centre For Reproductive and Genetic Health, 230-232 Great Portland St, London, W1W 5QS, UK.

3

IGENOMIX, 40 Occam Road, Guildford, Surrey, GU2 7YG, UK.

4

Clinical Department, The Centre For Reproductive and Genetic Health, 230-232 Great Portland St, London, W1W 5QS, UK.

Abstract

PURPOSE:

Does blastocyst morphology following euploid elective single embryo transfer (eSET) after preimplantation genetic testing for aneuploidies (PGT-A) via next generation sequencing impact clinical outcome?

METHODS:

Two hundred ninety-six patients underwent PGT-A. Of 1549 blastocysts, 1410 blastocysts had a conclusive result after PGT-A and were included for analysis. An eSET policy was followed in a frozen embryo replacement cycle. A total of 179 euploid blastocysts were thawed and transferred. Clinical outcomes were categorized in four different embryo quality groups: excellent, good, average and poor.

RESULTS:

Euploidy rate was 19/36 (52.7%, 95% CI 37-68), 199/470 (42.3%, 95% CI 38-47), 156/676 (23.0%, 95% CI 20-26) and 39/228 (17.1%, 95% CI 13-23) in the excellent, good, average and poor quality blastocyst groups, respectively. Fitted logistic regression analysis taking into account the following covariables: female, age, embryo chromosomal status and day of blastocyst development/biopsy showed that morphology was predictive of the comprehensive chromosome screening result (p < 0.05). A logistic regression analysis was also performed on clinical outcomes taking into account the effect of blastocyst morphology and day of blastocyst development/biopsy. None of the parameters were shown to be significant, suggesting morphology and day of blastocyst development/biopsy do not reduce the competence of euploid embryos (p > 0.05).

CONCLUSIONS:

After eSET, implantation rate was 80-86%; live birth rate per embryo transfer was 60-73% and clinical miscarriage rate was found to be < 10% and were not significantly affected by the embryo morphology. Results are concordant with those reported when using aCGH and highlights the competence of poor-quality euploid embryos.

傳統觀念認為Day3 (HCG後70-78h)胚胎分裂速度過達12胚葉細胞通常預後不佳
本篇反駁此觀點
事實上胚胎分裂ㄉ速度  型態  在Day3 通常可說大勢底定 
Day 3 通常分裂為8-10 cell   速度略快是可被接受
速度慢於6 cell 的胚胎幾乎無法著床

J Assist Reprod Genet. 2019 Sep 2. doi: 10.1007/s10815-019-01574-y. [Epub ahead of print]

Deconstructing the myth of poor prognosis for fast-cleaving embryos on day 3. Is it time to change the consensus?

Pons MC1, Carrasco B2, Parriego M2, Boada M2, González-Foruria I2, Garcia S2, Coroleu B2, Barri PN2, Veiga A2,3.

Author information

1

Reproductive Medicine Service, Dexeus Mujer, Hospital Universitari Dexeus, Gran Via Carles III, 71-75, 08028, Barcelona, Spain. carpon@dexeus.com.

2

Reproductive Medicine Service, Dexeus Mujer, Hospital Universitari Dexeus, Gran Via Carles III, 71-75, 08028, Barcelona, Spain.

3

Barcelona Stem Cell Bank, Centre of Regenerative Medicine in Barcelona, Hospital Duran i Reynals, Gran Via de l' Hospitalet 199, 08908, Hospitalet de Llobregat, Spain.

Abstract

PURPOSE:

To determine the developmental competence of fast-cleaving D3 embryos.

METHODS:

Retrospective study including 4028 embryos from 513 PGT-A cycles performed between July 2014 and June 2017. Embryos were cultured in time-lapse incubators and biopsied at blastocyst stage. Embryos were classified in groups according to the number of cells on D3 (from 2-cell to ≥13 -cell and compacted). A generalized linear mixed model adjusted for confounding factors was performed to assess the chance to give rise to an euploid blastocyst in each group compared with the chance of 8-cell embryos. Implantation and live birth rates were also analyzed.

RESULTS:

The statistical analysis showed that embryos with 9 to 11 cells had a slightly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.77 (0.61-0.96)) while embryos with more than 11 cells were found to be just as likely to give rise to an euploid blastocyst as the 8-cell embryos (OR (95% CI) 1.20 (0.92-1.56)). Conversely, slow-cleaving embryos had a significantly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.31 (0.24-0.39)). Moreover, euploid blastocysts derived from fast-cleaving embryos and from 8-cell embryos exhibit similar live birth rates. No significant differences were found in the chance to give rise a live birth between 8-cell and 9- to 11-cell embryos (OR (95% CI) 1.23 (0.70-2.15)) and > 11-cell embryos (OR (95% CI) 1.09 (0.57-2.09)).

CONCLUSIONS:

Embryos with more than 11 cells exhibit similar developmental competence to 8-cell embryos. Their poor prognosis should be reconsidered.

胚胎植入前15分打少量HCG 500 iu入子宮腔
----無法明顯提高活產率

Arch Gynecol Obstet. 2018 Dec;298(6):1061-1069. doi: 10.1007/s00404-018-4923-1. Epub 2018 Oct 5.

Effect of intrauterine injection of human chorionic gonadotropin before fresh embryo transfer on IVF and ICSI outcomes: a meta-analysis.

Hou W1, Shi G1, Cai B1, Ding C1, Song J1, Zhang X1, Xu Y2.

Author information

1

Reproductive Medical Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

2

Reproductive Medical Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. xuyanwen663000@126.com.

Abstract

PURPOSE:

This analysis was performed to evaluate the effects of intrauterine injection of human chorionic gonadotropin (hCG) before fresh embryo transfer (ET) on the outcomes of in vitro fertilization and intracytoplasmic sperm injection.

METHODS:

Randomized controlled trials (RCTs) were identified by searching electronic databases. The outcomes of live birth, clinical pregnancy, implantation, biochemical pregnancy, ongoing pregnancy, ectopic pregnancy, and miscarriage between groups with and without hCG injections were analyzed. Summary measures were reported as risk ratios (RR) with 95% confidence intervals.

RESULTS:

Six RCTs on fresh embryo transfer (ET) were included in the meta-analysis. A total of 2759 women undergoing fresh ET were enrolled (hCG group n = 1429; control group n = 1330). Intrauterine injection of hCG significantly increased rates of biochemical pregnancy (RR 1.61) and ongoing pregnancy (RR 1.58) compared to controls. However, there were no significant differences in clinical pregnancy (RR 1.11), implantation (RR 1.17), miscarriage (RR 0.91), ectopic (RR 1.65) or live birth rates (RR 1.13) between the hCG group and control group.

CONCLUSION:

The current evidence for intrauterine injection of hCG before fresh ET does not support its use in an assisted reproduction cycle.

胚胎植入前15分打少量HCG 500 iu入子宮腔可提高胚胎著床率  (22-->31%),  活產率 (30-->44%)

Fertil Steril. 2019 Jul;112(1):89-97.e1. doi: 10.1016/j.fertnstert.2019.02.027.

Intrauterine injection of human chorionic gonadotropin before embryo transfer can improve in vitro fertilization-embryo transfer outcomes: a meta-analysis of randomized controlled trials.

Gao M1, Jiang X2, Li B3, Li L1, Duan M2, Zhang X4, Tian J5, Qi K6.

Abstract

OBJECTIVE:

To evaluate whether intrauterine injection of hCG before embryo transfer can improve IVF-ET outcomes.

DESIGN:

Meta-analysis.

SETTING:

Not applicable.

PATIENT(S):

Infertile women who underwent IVF-ET and received an intrauterine injection of hCG before ET.

INTERVENTION(S):

Infertile women treated with or without intrauterine hCG injection before ET.

MAIN OUTCOME MEASURE(S):

The primary outcomes were live birth rate (LBR), ongoing pregnancy rate (OPR), and clinical pregnancy rate (CPR), and the secondary outcomes were implantation rate (IR) and miscarriage rate (MR). Odds ratios with 95% confidence intervals (CIs) and successful ET rates were pooled to determine the effects of hCG on IVF-ET outcomes.

RESULT(S):

Fifteen randomized controlled trials (RCTs) with a total of 2,763 participants were included. Infertile women in the experimental group (treated with intrauterine hCG injection before ET) exhibited significantly higher LBR (44.89% vs. 29.76%), OPR (48.09% vs. 33.42%), CPR (47.80% vs. 32.78%), and IR (31.64% vs. 22.52%) than those in the control group (intrauterine injection of placebo or no injection). Furthermore, MR was significantly lower (12.45% vs. 18.56%) in the experimental group than in the control group.

CONCLUSION(S):

The findings of this meta-analysis indicate that intrauterine injection of hCG can improve LBR, OPR, CPR, and IR after IVF-ET cycles. In addition, different timing and dosages of hCG administration may exert different effects on IVT-ET outcomes. Notably, infertile women treated with 500 IU hCG within 15 minutes before ET can achieve optimal IVF-ET outcomes.

傳統PGS須使用ICSI授精
本篇指出IVF受精之胚胎仍可使用PGS偵測
IVF形成胚胎染色體鑲嵌比例較高 IVF (25.9%) versus ICSI (20.9%).

J Assist Reprod Genet. 2019 Jan;36(1):153-157. doi: 10.1007/s10815-018-1347-6. Epub 2018 Oct 25.

Minimizing mosaicism: assessing the impact of fertilization method on rate of mosaicism after next-generation sequencing (NGS) preimplantation genetic testing for aneuploidy (PGT-A).

Palmerola KL1,2, Vitez SF3, Amrane S4,3, Fischer CP5, Forman EJ4.

Author information

1

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Columbia University Medical Center, 5 Columbus Circle, PH, New York, NY, 10019, USA. Kdl2112@cumc.columbia.edu.

2

Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 622 West 168th Street, PH 16-66, New York, NY, 10032, USA. Kdl2112@cumc.columbia.edu.

3

Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 622 West 168th Street, PH 16-66, New York, NY, 10032, USA.

4

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Columbia University Medical Center, 5 Columbus Circle, PH, New York, NY, 10019, USA.

5

IVI/RMA New Jersey, 140 Allen Road, Basking Ridge, NJ, 07920, USA.

Abstract

PURPOSE:

Advances in preimplantation genetic testing (PGT) have led to practice changes in assisted reproductive technologies (ART), enabling fertility centers to transfer single embryos while maintaining excellent ongoing pregnancy rates, reducing miscarriage rates, and dramatically reducing ART-associated multiple pregnancies. The introduction of next-generation sequencing (NGS) allows PGT laboratories to assess for embryo mosaicism-although the true incidence and reproductive potential of predicted mosaic embryos are controversial. Due to concern for genetic contamination from other spermatozoa, most reference laboratories require use of intracytoplasmic sperm injection (ICSI) for single gene preimplantation genetic diagnosis (PGT-M). However, in PGT for aneuploidy (PGT-A), conventional insemination (IVF) is typically permissible. The purpose of this study was to evaluate rates of euploid, aneuploid, and mosaic in trophectoderm biopsy samples from embryos in IVF versus ICSI PGT-A cycles. Secondary aims were to assess sex ratio, and subtypes of aneuploidy and mosaicism in IVF versus ICSI PGT-A cycles.

METHODS:

We performed a retrospective review of women undergoing PGT-A at a single academic fertility center from July 1, 2015, to September 1, 2017. In all cycles, PGT-A was performed via trophectoderm biopsy on day 5 or 6 and analyzed using NGS at a single reference lab. We collected and compared patient demographics, fertility testing, cycle characteristics, and PGT-A outcomes between IVF and ICSI cycles.

RESULTS:

Three hundred two PGT-A cycles were included for analysis: 75 IVF and 227 ICSI cycles, resulting in 251 IVF and 724 ICSI biopsied blastocysts. Mean oocyte age of included cycles was 38.6 years (IVF) and 38.5 years (ICSI), p = 0.85. Baseline characteristics of IVF and ICSI PGT-A cycles were similar with the exception of semen parameters: IVF cycles had higher sperm concentration and total motility compared to ICSI cycles. PGT-A outcomes did not differ between IVF and ICSI cycles: euploid 27.9% (IVF) versus 30% (ICSI); aneuploid 45.4% (IVF) versus 43.1% (ICSI); no result 4.4% (IVF) versus 6.2% (ICSI). Though not significant, we identified a trend toward higher rate of mosaicism in IVF (25.9%) versus ICSI (20.9%). Among mosaic embryos, a lower percentage of simple mosaic embryos resulted from IVF (53.8%) versus ICSI (70.2%). Among aneuploid embryos, a non-significant higher percentage of complex aneuploidy resulted from IVF (16.3%) versus ICSI (9%). IVF resulted in a non-significant higher proportion of cycles with no transferrable embryos (42.7%) versus ICSI (36.6%). Numerical and sex chromosome involvement in mosaicism and aneuploidy were similar between IVF and ICSI cycles.

CONCLUSION:

IVF and ICSI NGS PGT-A have similar rates of euploid, aneuploid, and no result embryos, though IVF may result in higher rates of mosaicism and demonstrates differences in proportions of mosaic and aneuploid subtypes compared to ICSI. ICSI may be preferable to conventional insemination to minimize the rate of mosaic results in NGS PGT-A cycles.

全球大規模 PGS  顯示異常ㄉ胚胎植入後仍有相當比例能產下正常胚胎
PGS之準確性與適用性仍屬爭議

J Assist Reprod Genet. 2019 Aug;36(8):1599-1607. doi: 10.1007/s10815-019-01510-0. Epub 2019 Jun 24.

Worldwide live births following the transfer of chromosomally "Abnormal" embryos after PGT/A: results of a worldwide web-based survey.

Patrizio P1, Shoham G2, Shoham Z3,4, Leong M5, Barad DH6,7, Gleicher N6,7,8,9.

Author information

1

Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Reproductive Medicine and Infertility, Yale University, New Haven, CT, USA. pasquale.patrizio@yale.edu.

2

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

3

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Kaplan Hospital, Rehovot, Israel.

4

Hadassah School of Medicine, Hebrew University, Jerusalem, Israel.

5

IVF Clinic, The Women's Clinic, 12F, Central Tower, 28 Queen's Road Central, Central, Hong Kong.

6

The Center for Human Reproduction, New York, NY, USA.

7

The Foundation for Reproductive Medicine, New York, NY, USA.

8

Laboratory for Stem Cell and Molecular Embryology, The Rockefeller University, New York, NY, USA.

9

The Department of Obstetrics and Gynecology, Vienna School of Medicine, Vienna, Austria.

Abstract

PURPOSE:

Preimplantation genetic testing for aneuploidy (PGT-A) has become increasingly controversial since normal euploid births have been reported following transfer of embryos diagnosed as "abnormal." There is an increasing trend in transferring "abnormal" embryos; but it is still unknown how many IVF centers transfer "abnormal" embryos and with what efficiency.

METHODS:

We performed a worldwide web-survey of IVF centers to elucidate PGT-A related practice patterns including transfer of human embryos found "abnormal" by PGT-A. Participating centers reflected in vitro fertilization (IVF) cycles in the USA, Canada, Europe, Asia, South America, and Africa.

RESULTS:

One hundred fifty-one IVF centers completed the survey; 125 (83%) reported utilization of PGT-A. Europe had the highest utilization (32.3%), followed by the USA and Canada combined at 29.1%. The leading indications for PGT-A were advanced maternal age (77%), followed by recurrent implantation failure (70%), unexplained pregnancy loss (65%), and sex determination (25%); 14% of respondents used PGT-A for all of their IVF cycles; 20% of IVF units reported transfers of chromosomally "abnormal" embryos, and 56% of these took place in the USA, followed by Asia in 20%. Remarkably, 106 (49.3%) cycles resulted in ongoing pregnancies (n = 50) or live births (n = 56). Miscarriages were rare (n = 20; 9.3%).

CONCLUSIONS:

The transfers of "abnormal" embryos by PGT-A offered robust pregnancy and live birth chances with low miscarriage rates. These data further strengthen the argument that PGT-A cannot reliably determine which embryos should or should not be transferred and leads to disposal of many normal embryos with excellent pregnancy potential.