PGT
無法明顯下降胚胎染色體異常之流產
無法明顯下降習慣性流產
---PGT無法明顯提高活產率

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.

Sato T1, Sugiura-Ogasawara M1, Ozawa F1, Yamamoto T2, Kato T3, Kurahashi H3, Kuroda T4, Aoyama N4, Kato K4, Kobayashi R5, Fukuda A5, Utsunomiya T6, Kuwahara A7, Saito H8, Takeshita T9, Irahara M7.

Author information

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.

ICM之組成

可區分為epiblast & primitive endoderm

epiblast日後形成胚胎

 primitive endoderm日後形成胎盤

胚胎切片遠離ICM才可避免傷及epiblast

Dev Cell. 2019 Jul 22;50(2):139-154.e5. doi: 10.1016/j.devcel.2019.05.024. Epub 2019 Jun 13.

Epiblast Formation by TEAD-YAP-Dependent Expression of Pluripotency Factors and Competitive Elimination of Unspecified Cells.

Hashimoto M1, Sasaki H2.

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Abstract

The epiblast is a pluripotent cell population first formed in preimplantation embryos, and its quality is important for proper development. Here, we examined the mechanisms of epiblast formation and found that the Hippo pathway transcription factor TEAD and its coactivator YAP regulate expression of pluripotency factors. After specification of the inner cell mass, YAP accumulates in the nuclei and activates TEAD. TEAD activity is required for strong expression of pluripotency factors and is variable in the forming epiblast. Cells showing low TEAD activity are eliminated from the epiblast through cell competition. Pluripotency factor expression and MYC control cell competition downstream of TEAD activity. Cell competition eliminates unspecified cells and is required for proper organization of the epiblast. These results suggest that induction of pluripotency factors by TEAD activity and elimination of unspecified cells via cell competition ensure the production of an epiblast with naive pluripotency.

Fig. 1. Organization of a preimplantation mouse embryo (late blastocyst).
The pluripotent epiblast cells produce body of embryo. The mechanism, by which all the epiblast cells aquire high quality, has been unknown.

傳統胚胎冷凍或植入選擇Day3  Day 5
本篇指出凍胚解凍亦可選擇Day 4桑葚體冷凍解凍植入 結果比Day 3 8-16cell更佳

J Assist Reprod Genet. 2020 Feb 19. doi: 10.1007/s10815-020-01708-7. [Epub ahead of print]

Morula transfer achieves better clinical outcomes than post-thawed cleavage embryos after overnight culture in frozen embryo transfer (FET) cycles.

PURPOSE:

This study aimed to investigate the clinical outcomes of morula stage transfer derived from post-thawed cleavage embryos undergoing overnight culture in frozen embryo transfer (FET) cycles.

METHODS:

We performed a retrospective study that included 392 FET cycles with 784 thawed embryos undergoing overnight culture between January 2014 and December 2018. Embryos were divided into three groups in terms of their status: 8-16 cells without morula (group I), one morula (group II), and two morulae (group III). The clinical outcomes of these cycles were then compared between the three groups. Logistic regression analysis was performed to control for confounders.

RESULTS:

Group III was associated with a significantly higher clinical pregnancy rate (odds ratio [OR] 2.35; 95% confidence interval [CI] 1.29-4.27; P = 0.005), implantation rate (OR 3.00; CI 1.75-5.16; P < 0.001), multiple pregnancy rate (OR 4.91; CI 2.11-11.40; P < 0.001), and live birth rate (OR 1.96; CI 1.10-3.49; P = 0.022) than group I. Group II had a higher live birth rate than group I after adjustment (OR 1.70; CI 1.04-2.79; P = 0.035). There was no difference in the rate of premature delivery when compared across the three groups after adjustment.

CONCLUSION:

The transfer of morula stage embryos following the overnight culture of post-thawed cleavage embryos led to an improvement in the clinical outcomes of FET cycles. It is important to reduce the number of morula embryos transferred in order to achieve a singleton pregnancy.

 凍胚植入當天 ，P4濃度對懷孕率無明顯影響  (P4 levels < 10 ng/mL and ≥ 10 ng/mL)＿

J Assist Reprod Genet. 2020 Feb 10. doi: 10.1007/s10815-020-01713-w. [Epub ahead of print]

Do serum progesterone levels on day of embryo transfer influence pregnancy outcomes in artificial frozen-thaw cycles?

PURPOSE:

The purpose of this study is to investigate whether progesterone (P4) levels on the day of frozen-thawed embryo transfer (FET) to a hormonally prepared endometrium correlate with pregnancy outcomes.

METHODS:

This is a large retrospective cohort analysis comprising of N = 2010 FETs. In these cycles, P4 levels on the day of transfer were assessed in relation to pregnancy outcomes. A threshold of 10 ng/mL was used to simulate currently accepted levels for physiological corpus luteal function. Biochemical pregnancy, clinical pregnancy, and live birth rates were compared between those with P4 levels above and below this threshold. Analyses using transfer day P4 thresholds of 5 ng/mL and 20 ng/mL were then completed to see if these could create further prognostic power.

RESULTS:

When comparing FET outcomes in relation to P4 levels < 10 ng/mL and ≥ 10 ng/mL, we observed no differences in biochemical pregnancy rates (39.53% vs. 40.98%, p = 0.52), clinical pregnancy rates (20.82 vs. 22.78, p = 0.30), and live birth rates (14.25 vs. 16.21 p = 0.23). In patients whose P4 met the threshold of 20 ng/mL, there was similarly no statistically significant improvement in pregnancy outcomes. While there was no difference for biochemical or clinical pregnancy rates, a statistically significant improvement in live birth rates was observed for those with a transfer day P4 level ≥ 5 ng/mL.

CONCLUSIONS:

We demonstrated that P4 levels at or above 10 ng/mL on the day of FET do not confer a statistically significant improvement in pregnancy outcomes. P4 below 5 ng/mg was associated with lower live birth rates suggesting that there is a threshold below which it is difficult to salvage FET cycles.

IVF-ET黃體素使用

progesterone vaginal pessaries 400 mg bid vs. progesterone 8% vaginal gel (90 mg od) 

臨床懷孕率並無差異 (38.1 vs 40.4%)

Hum Reprod. 2020 Feb 19. pii: dez261. doi: 10.1093/humrep/dez261. [Epub ahead of print]

Efficacy, safety and tolerability of progesterone vaginal pessaries versus progesterone vaginal gel for luteal phase support after in vitro fertilisation: a randomised controlled trial.

Saunders H1, Khan C2, D'Hooghe T3,4,5, Magnúsdóttir TB6, Klingmann I7, Hrafnsdóttir S6; vaginal progesterone luteal phase support post IVF study group.

Author information

Abstract

STUDY QUESTION:

Are progesterone vaginal pessaries 400 mg twice a day (bid) non-inferior to progesterone vaginal gel (90 mg) once a day (od) in the primary endpoint of clinical pregnancy rate after 38 days of luteal phase support in women undergoing in vitro fertilisation (IVF)?

SUMMARY ANSWER:

Non-inferiority of progesterone vaginal pessaries 400 mg bid to progesterone 8% vaginal gel (90 mg od) was shown for clinical pregnancy rate after 38 days of luteal phase support.

WHAT IS KNOWN ALREADY:

To maximise successful embryo transfer after IVF, additionally administered progesterone is used for proper endometrium transformation in the luteal phase. Vaginally administered progesterone results in adequate secretory transformation of the endometrium.

STUDY DESIGN, SIZE, DURATION:

This multicentre, multinational, open, randomised, two-parallel group, non-inferiority Phase 3 clinical trial was carried out at 17 study sites in five European countries (Belgium, Bulgaria, Czech Republic, Hungary and Serbia) between October 2013 and August 2014. An interactive web response system (IWRS) was implemented for treatment allocation at the sites. Power analysis, based on the assumptions of a non-inferiority margin of -9%, a significance level of α 2.5% (one-sided), power 90%, at a reference pregnancy rate for the progesterone vaginal gel group of 30%, as well as applying a dropout rate of 10%, yielded a total number of 766 patients to be randomised.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Women aged between 18 and 40 years with a clinical indication for IVF/intracytoplasmic sperm injection (ICSI) and embryo transfer were eligible to participate. The clinical pregnancy rate was assessed by fetal heart movement measured by transvaginal ultrasound at day 38 (D38) (primary endpoint) and D70. Also assessed were biochemical pregnancy rate (assessed by serum β-hCG ≥25 IU/L), clinical implantation rates at D38, patient evaluation of vaginal bleeding and discharge (assessed by diary) and adverse event (AE) incidence, severity and relationship to study medication.

MAIN RESULTS AND THE ROLE OF CHANCE:

A total of 769 female patients were randomised to progesterone 400 mg vaginal pessaries bid (n = 385, 50.1%) or progesterone 90 mg vaginal gel od (n = 384, 49.9%). Patients receiving progesterone vaginal pessaries and progesterone vaginal gel were comparable in demographics, baseline characteristics and number of retrieved oocytes. In the full analysis set (FAS; n = 369 progesterone vaginal pessaries and n = 368 progesterone vaginal gel), clinical pregnancy rates on D38 were 38.3% for progesterone vaginal pessaries and 39.9% for progesterone vaginal gel. In the per protocol analysis set (PP; n = 357 progesterone vaginal pessaries and n = 356 progesterone vaginal gel), clinical pregnancy rates on D38 were 38.1% for progesterone vaginal pessaries and 40.4% for progesterone vaginal gel. For the differences in pregnancy rates between the progesterone vaginal pessaries group and the progesterone vaginal gel, the lower limit of the 97.5% CI was -8.6 and -9.5% for the FAS and PP datasets, respectively. The original prespecified non-inferiority margin of -9% was thus met in the FAS dataset but was marginally below this in the PP dataset. However, the pregnancy rate of the comparator was higher than the anticipated rate of 30%, and a predetermined logistic regression model including treatment group, country and age group effects without interaction terms showed non-inferiority of progesterone vaginal pessaries to progesterone vaginal gel for both the FAS and PP populations, in that the lower limits of the 95% CIs were above 0.7 for both analyses. As a result of this, the relevant authorities accepted to widen the acceptable non-inferiority margin to -10%, and as such both the FAS and PP populations succeeded in showing non-inferiority. Biochemical pregnancy and clinical implantation rates were comparable for both treatments. Both treatment groups showed similar high compliance throughout the study, and the safety profiles were also comparable between the groups. Drug-related AEs occurred with frequencies of 15.1% with progesterone vaginal pessaries and 14.4% with progesterone vaginal gel.

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.

子宮內膜異位瘤之病患  以基礎濾泡(antral follicle count)比AMH更有效於評估卵巢功能
子宮內膜異位瘤之病患 vs 正常卵巢病患，縱使AMH數值相同 ，子宮內膜異位瘤病患之卵子數目仍顯較少

J Obstet Gynaecol. 2019 May;39(4):516-521. doi: 10.1080/01443615.2018.1533542. Epub 2019 Feb 11.

Does the anti-Müllerian hormone truly reflect ovarian response in women with endometrioma?

Inal ZO1, Engin Ustun Y2, Yilmaz N2, Aktulay A2, Bardakci Y3, Gulerman C2.

Abstract

In this study, our aim was to determine which factor is more correlated with the number of oocytes retrieved in patients with endometrioma compared with controls undergoing in vitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI) cycles: antral follicle count (AFC) or anti-Müllerian hormone (AMH). A total of 60 women with endometrioma and a control population of 60 women without endometrioma in the same period were randomly selected underwent the injection IVF-ICSI treatment. No significant differences were found between the groups in terms of age (28.78 ± 3.49 vs. 29.52 ± 2.47, p = .187), body mass index (23.62 ± 2.05 vs. 23.91 ± 2.11, p = .449), duration of infertility [(3 (2-4) vs. 3 (2-3), p = .139)], AMH level (1.52 ± 0.51 vs. 1.32 ± 0.92, p = .133), duration of stimulation [(9 (9-10) vs. 10 (9-10), p = .135)], total gonadotropin dose [(2750 (2262.5-3337.5) vs. 2770 (2680-3562.5), p = .125)], endometrial thickness [(10 (10-11) vs. 10 (9-11), p = .463)], fertilisation rates (67.20 ± 18.04 vs. 62.28 ± 17.13, p = .123), grade I embryo (43.3% vs. 30%, p = .185), clinical pregnancy rates (40% vs. 26.7%, p = .123), and the perinatal outcomes between the groups. The AFC was higher in the controls than in those with endometrioma (9.20 ± 1.80 vs. 6.32 ± 2.04, p < .001). The number of oocytes retrieved was also higher in the controls than in those with endometrioma [(7 (6-8) vs. 4 (4-5.75), p < .001)]. We found that women with endometrioma had a significantly lower number of oocytes retrieved than the controls despite the same AMH levels in both groups. AFC is a better marker of ovarian response than AMH in women with endometrioma undergoing IVF-ICSI. Impact statement What is already known on this subject? Utilising the ovarian reserve is important in the success of ovarian stimulation and in evaluating the success of assisted reproductive technologies. The anti-Müllerian hormone (AMH) level and the antral follicle count (AFC) are widely used in the prediction of ovarian functional reserve and response. However, no perfect marker exists in the evaluation of ovarian reserve and ovarian response. What do the results of this study add? Our study demonstrated that women with endometrioma have a significantly lower number of oocytes retrieved than the controls, despite the same AMH levels in both groups; which strongly suggests that AFC is a better reflection of ovarian response than AMH in women with endometrioma undergoing an in vitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI). What are the implications of these findings for clinical practice and/or further research? This important issue has been reviewed and discussed for years, however, the conclusions are still controversial. Additional research is needed to understand which ovarian reserve test could better predict ovarian response outcome?

精蟲與20%濾泡液共同培養可提升精蟲活動力&下降精蟲DNA異常率

J Assist Reprod Genet. 2019 Dec 5. doi: 10.1007/s10815-019-01643-2. [Epub ahead of print]

Co-incubation of spermatozoa with human follicular fluid reduces sperm DNA fragmentation by mitigating DNase activity in the seminal plasma.

Dorado-Silva M1, Bartolomé-Nebreda J2, Sánchez-Martín P1, Johnston S3, Gosálvez J2.

Author information

1

Ginemed, Clinic for Assisted Reproduction, Sevilla, Spain.

2

Unit of Genetics, Department of Biology, Universidad Autónoma de Madrid, Madrid, Spain.

3

School of Agriculture and Food Sciences, University of Queensland, Gatton, Australia. s.johnston1@uq.edu.au.

Abstract

PURPOSE:

To examine the effect of co-incubating spermatozoa with human follicular fluid (HFF) on the rate of sperm DNA fragmentation.

METHODS:

This prospective study used semen (n = 23) and HFF from oocyte donors (n = 23). Liquified semen was divided into four aliquots: (1) neat semen (NEAT), (2) seminal plasma removed and replaced with sperm media (HTF) containing 0% (FF0), (3) 20% (FF20), or (4) 50% (FF50) HFF. Sperm motility and DNA fragmentation (SDF) were assessed following 24 h of incubation at 37 °C. Pro-oxidant capacity of HFF and seminal plasma and the effect of HFF on seminal plasma DNase activity was assessed in a sub-sample of 10 ejaculates.

RESULTS:

Sperm motility was higher after 3 h of incubation in media that contained HFF compared to the NEAT sample or when sperm was diluted in media without HFF. r-SDF (increase of SDF per time unit) values after 24 h of incubation for NEAT, FF0, FF20 and FF50 were 0.91, 0.69, 0.25 and 0.36, respectively. While pro-oxidant capacity of seminal plasma samples showed large variation (mean: 94.6 colour units; SD 65.4), it was lower and more homogeneous in FF samples (mean: 29.9 colour units; SD: 6.3). Addition of HFF to seminal plasma appeared to inhibit DNase activity.

CONCLUSION:

While differences exist in the pro-oxidant capacity of seminal plasma of patients, sperm DNA integrity was preserved with addition of HFF to sperm media, irrespective of the level of pro-oxidant capacity. DNase activity in the original seminal plasma was abolished after HFF co-incubation.