2016年11月30日

囊胚期胚胎染色體異常率(aneuploidy)高達44%
生長速度較慢(day6 才達囊胚)之囊胚期胚胎染色體異常率高達70%


 2016 Sep;33(3):398-403. doi: 10.1016/j.rbmo.2016.06.005. Epub 2016 Jun 23.

Does slow embryo development predict a high aneuploidy rate on trophectoderm biopsy?

Abstract

The aneuploidy rates in expanded blastocysts biopsied on days 5 and 6 development were assessed in women undergoing IVF followed by array comparative genomic hybridization. This study included 1171 expanded blastocysts from 465 patients. Among the 465 patients, 215 and 141 underwent embryo biopsy on day 5 and day 6 (46.2% and 30.3%, respectively), and 109 underwent biopsy on both days 5 and 6 (23.4%). The cycles of 206 women were cancelled because only aneuploidy embryos were present (44.3%). The aneuploid embryos were classified according to the type as single, double or complex aneuploidy. No differences were observed in the distributions of these three categories according to the day of the biopsy. The aneuploidy rate was also evaluated according to maternal age, and was found to be higher in older patients; however, no differences in this rate were detected between embryos biopsied on days 5 and 6 according to maternal age. Biopsy was carried out when blastocysts reached the expanded stage. The embryos biopsied on day 6 had a higher rate of aneuploidy (69.9%) than those biopsied on day 5 (61.4%); however, the euploid embryos transferred had similar chances for successful and healthy gestation.
IVF病患LH濃度過低( ≤0.8 mIU/ml at any time during the cycle),胚胎植入後較易流產


 2016 Oct;33(4):449-457. doi: 10.1016/j.rbmo.2016.07.001. Epub 2016 Jul 21.

Frequency of low serum LH is associated with increased early pregnancy loss in IVF/ICSI cycles.

Abstract

The role of LH during ovarian stimulation remains uncertain. Previous studies defined the low LH group using a single LH measurement on a predefined day of stimulation possibly not reflecting the entire follicular phase. This study retrospectively collected data from 619 IVF/ICSI cycles with GnRH antagonist and recombinant FSH. The low LH group was defined as LH concentration ≤0.8 mIU/ml at any time during the cycle. Pregnancy results were compared between patients with one episode of low LH or more than two episodes of low LH (study group) and those without low LH (control group). There was no difference in fertilization rates between the two groups (67.5 ± 1.7% versus 68.8 ± 1.0%, respectively). The implantation rates (20.4% versus 25.2%), clinical pregnancy rates (43.9% versus 45.2%) and live-birth rates (LBR) (23.7% versus 30.4%) appeared lower in the study group, but the differences were not significant. In the study group, there were significantly increased early pregnancy loss rates (31.1% versus 16.3%, P = 0.012). The odds of early pregnancy loss increases by 1.55 fold for increased episodes of low serum LH (P = 0.029). Whether the adverse outcome is due to impaired oocyte quality or an endometrial component deserves further investigation.
中國病患AMH數值顯示
AMH >2.6屬卵巢高度反應
AMH 2.6-1.1屬卵巢中度反應
AMH <1.1屬卵巢低度反應

 2016 Oct;33(4):506-512. doi: 10.1016/j.rbmo.2016.07.003. Epub 2016 Jul 25.

Anti-Müllerian hormone for prediction of ovarian response in Chinese infertile women undergoing IVF/ICSI cycles: a prospective, multi-centre, observational study.

Li R1Gong F2Zhu Y3Fang W4Yang J5Liu J6Hu L7Yang D8Liang X9Qiao J10.

Abstract

This study explored the correlation between serum anti-Müllerian hormone (AMH) concentration and the number of retrieved oocytes after ovarian stimulation in Chinese infertile women undergoing assisted reproductive technology treatment and AMH cut-off values predicting low and high ovarian response. This was a prospective, multi-centre, observational study. A total of 615 subjects were included in nine assisted reproductive centres in China for outcome analysis. Subjects received assisted reproductive technology treatment and used recombinant human FSH (r-HFSH) or r-HFSH plus recombinant LH (rLH) for ovarian stimulation according to conventional treatment regimens. The main outcome variables were correlations between AMH and the number of retrieved oocytes and the cut-off values of AMH predicting low and high ovarian response. Serum AMH concentration was positively correlated with the number of oocytes retrieved in Chinese infertile women treated with IVF/intracytoplasmic sperm injection (ICSI) (Pearson correlation coefficient = 0.4754, P < 0.0001). The optimal AMH cut-off value was 2.6 ng/ml (sensitivity: 81.28%, specificity: 59.51%) in predicting high and normal response, and 1.1 ng/ml (sensitivity: 52.27%, specificity: 87.23%) in predicting low and normal response. In conclusion, serum AMH concentration can be used as a biomarker to predict ovarian response in Chinese infertile women treated with assisted reproductive technology.
動物實驗顯示,抑制血小板藥劑(Ozagrel, a TXA2 synthase inhibitor)可應用於抑制子宮內膜異位


 2016 Oct;33(4):484-499. doi: 10.1016/j.rbmo.2016.07.007. Epub 2016 Jul 26.

Anti-platelet therapy is efficacious in treating endometriosis induced in mouse.

Abstract

In light of recent findings showing that platelets play important roles in the development of endometriosis in general and in fibrogenesis in particular, this study investigated the efficacy of Ozagrel, a TXA2 synthase inhibitor, in a murine model of endometriosis. In addition, another mouse experiment was conducted to evaluate the effect of timing of platelet depletion and of sequential depletion of platelets and macrophages on the development of endometriosis. It was found that both the Ozagrel treatment and different platelet depletion schemes resulted in significant reduction in lesion growth (all P-values <0.01) along with improved hyperalgesia in mice with induced endometriosis. They also significantly reduced the expression of markers of proliferation, angiogenesis, inflammation and fibrosis as well as decreased macrophage infiltration in endometriotic lesions (all P-values <0.05). Compared with untreated mice, pre-emptive depletion of platelets as well as platelet depletion after induction resulted in significant reduction in lesion weight (both P-values <0.001), while sequential depletion of platelets and macrophages yielded similar reduction. These results, in conjunction with other roles that platelets play in the development of endometriosis, strongly argue for the potential of anti-platelet therapy in treating endometriosis.
使用年輕去核捐贈卵子當受體,將受孕高齡病人之胚胎之原核PN取出後植入去核卵子中,形成胚胎植入後順利懷孕

 2016 Oct;33(4):529-533. doi: 10.1016/j.rbmo.2016.07.008. Epub 2016 Aug 1.

Pregnancy derived from human zygote pronuclear transfer in a patient who had arrested embryos after IVF.

Abstract

Nuclear transfer of an oocyte into the cytoplasm of another enucleated oocyte has shown that embryogenesis and implantation are influenced by cytoplasmic factors. We report a case of a 30-year-old nulligravida woman who had two failed IVF cycles characterized by all her embryos arresting at the two-cell stage and ultimately had pronuclear transfer using donor oocytes. After her third IVF cycle, eight out of 12 patient oocytes and 12 out of 15 donor oocytes were fertilized. The patient's pronuclei were transferred subzonally into an enucleated donor cytoplasm resulting in seven reconstructed zygotes. Five viable reconstructed embryos were transferred into the patient's uterus resulting in a triplet pregnancy with fetal heartbeats, normal karyotypes and nuclear genetic fingerprinting matching the mother's genetic fingerprinting. Fetal mitochondrial DNA profiles were identical to those from donor cytoplasm with no detection of patient's mitochondrial DNA. This report suggests that a potentially viable pregnancy with normal karyotype can be achieved through pronuclear transfer. Ongoing work to establish the efficacy and safety of pronuclear transfer will result in its use as an aid for human reproduction.

2016年11月29日

卵子細胞膜無彈性於施行ICSI後卵子壞死機率較高(24%)受孕率較低(65%)
但胚胎形成囊胚機率無明顯差異(60-65%),懷孕率無形顯差異(50%)

 2016 Sep 17. [Epub ahead of print]

Developmental ability of embryos produced from oocytes with fragile oolemma by intracytoplasmic sperm injection.

Abstract

PURPOSE:

In intracytoplasmic sperm injection (ICSI) of oocytes with a fragile oolemma (fragile oocytes), breakage can occur at injection. In this study, we produced embryos from oocytes with a fragile and normal oolemma (normal oocytes) by ICSI and compared their ability to be fertilized and develop in vitro. We also investigated whether fragile oocyte-derived embryos could implant after blastocyst transfer to determine whether fragile oocytes should be used for assisted reproductive technology treatment.

METHODS:

Oocytes were divided into three groups-normal oocytes from cycles containing no fragile oocytes (group A), normal oocytes from cycles containing at least one fragile oocyte (group B), and fragile oocytes (group C), and their fertilization abilities after ICSI and the developmental abilities of resultant embryos were compared.

RESULTS:

The fertilization rate in group C (65.3 %) was significantly (P < 0.01) lower than those in groups A (84.6 %) and B (86.9 %), and the degeneration rate in group C (24.2 %) was significantly (P < 0.01) higher than those in groups A (0.71 %) and B (0.28 %). However, there were no significant differences in the blastocyst formation rates (59.7-67.5 %) of embryos among the different groups. In addition, the pregnancy rate after transfer of blastocysts in group C (50.0 %) was not significantly different from those in groups A (35.6 %) and B (45.8 %).

CONCLUSIONS:

The fertilization ability after ICSI of fragile oocytes is lower than that of normal oocytes but the resultant embryos have the same developmental ability as those of normal oocyte-derived embryos.
time-lapse胚胎即時監測顯示,囊胚期胚胎在最後膨脹&破殼而出前會有2-4小時短暫收縮&囊胚腔縮小之現象

 2016 Sep 12. pii: S1472-6483(16)30503-X. doi: 10.1016/j.rbmo.2016.08.020. [Epub ahead of print]

Morphokinetics of human blastocyst expansion in vitro.

Abstract

Time-lapse imaging offers new tools to study dynamic processes of development such as blastocyst formation and expansion. This study quantitatively describes expansion in human blastocysts from donated oocytes. Measurements of hourly interval rate of changes in the blastocoel cross-sectional area revealed oscillatory pulses having 2-4 h periodicities. Two types of oscillations were distinguished. An E-Type ('expansion') had positive peak and positive or slightly negative trough interval rate of change values, and these characterized most of the expansion period. A C-type ('contraction') represented an infrequent but notable contraction of the blastocoel with loss of blastocoel fluid. These were reversible within 2-4 h in both groups and followed by further expansion. Therefore, oscillatory pulses are an intrinsic property of the trophectoderm. The zona seems to variably dampen the amplitude of these pulses. Expansion kinetics were compared between blastocysts with known positive (KID+) or negative (KID-) implantation outcomes. Regression analysis suggests that expansion may be relatively restricted in KID- embryos blastulating at relatively later times. These data extend observations in other mammalian systems and may provide information useful for clinical selection algorithms.
男性體重過重對精蟲品質有不良影響
男性體重過重造成精蟲數量減低,活動力減低,活力減低,型態異常增加,DNA碎片增加,ROS增加


 2016 Sep 16. pii: S1472-6483(16)30507-7. doi: 10.1016/j.rbmo.2016.08.023. [Epub ahead of print]

Does being overweight affect seminal variables in fertile men?

Abstract

The effect of being overweight on seminal variables was assesed in 165 fertile men. Participants were divided into three groups: fertile men with normal body mass index (BMI) (18.5-24.9 kg/m2), fertile overweight men (BMI 25-29.9 kg/m2) and fertile obese men (BMI >30 kg/m2). Medical history was taken, a clinical examination conducted. Semen analysis was undertaken and BMI measured. Seminal reactive oxygen species (ROS) was estimated by chemiluminescent assay, sperm vitality by the hypo-osmotic swelling test and sperm DNA fragmentation by propidium iodide staining with flowcytometry. Fertile obese men had significantly lower sperm concentration, progressive sperm motility and sperm normal morphology, with significantly higher seminal ROS and sperm DNA fragmentation compared with fertile normal-weight men and overweight men (all P < 0.05). BMI was negatively correlated with sperm concentration (r = -0.091; P = 0.014), progressive sperm motility (r = -0.697; P = 0.001), normal sperm morphology (r = -0.510; P = 0.001), sperm vitality (r = -0.586; P = 0.001), but positively correlated with sperm DNA fragmentation percentage (r = 0.799; P = 0.001) and seminal ROS (r = 0.673; P = 0.001). Increased BMI was found to affect semen parameters negatively even in fertile men.
體重超重可能會提高胚胎植入後流產之機率(14.2%>41.9%)


 2016 Oct 17. pii: S1472-6483(16)30555-7. doi: 10.1016/j.rbmo.2016.09.011. [Epub ahead of print]

Increased miscarriage of euploid pregnancies in obese women undergoing cryopreserved embryo transfer.

Abstract

Obesity is known to be associated with an increased risk of miscarriage after natural and assisted conception. Although most sporadic miscarriages are caused by genetic abnormalities, it is presently uncertain if genetics is also the underlying mechanism leading to increased pregnancy loss seen in obese women. Karyotyping of the products of conception suggests a reduced rate of fetal aneuploidy in miscarriages from obese compared with lean individuals. Karyotype analysis, however, is prone to false negative results because of inadvertent culture of maternal rather than fetal tissue. Therefore, to better analyse the effect of the genetic status on obesity-related miscarriage, we retrospectively analysed the outcomes 125 consecutive cryopreserved embryo transfer cycles resulting in a pregnancy after screening for genetic normality using comparative genomic hydridization. Lean individuals (body mass index 18.5-24.9 kg/m2) had a significantly lower rate of miscarriages (14.2%) than overweight (29.1%) or obese (41.9%) women (P = 0.001); this relationship remained significant (P = 0.023) even after adjusting for relevant confounders, e.g. maternal age, cause of infertility, number of previous IVF cycles, type of frozen embryo transfer cycle or past obstetric history. These results support a non-genetic cause for obesity-related miscarriage.
Leuplin acetat 1mg (=0.2ml)可用於破卵,破卵效果類似0.2 mg triptorelin & 10000 iu HCG


 2016 Oct 17. pii: S1472-6483(16)30557-0. doi: 10.1016/j.rbmo.2016.10.004. [Epub ahead of print]

Final oocyte maturation with two different GnRH agonists in antagonist co-treated cycles at risk of ovarian hyperstimulation syndrome.

Abstract

Triptorelin 0.2 mg and leuprolide 1 mg subcutaneous injections for triggering final follicular maturation were compared in patients with a high risk for ovarian hyperstimulation syndrome (OHSS). Infertile patients treated with GnRH antagonist protocol between January 2014 and March 2016 were recruited. Patients with high serum oestradiol levels on HCG day (>3000 pg/ml) indicating a risk of OHSS consisted of the study groups (A and B). Patients with serum oestradiol levels less than 3000 pg/ml consisted of the control group (C). A single injection of 0.2 mg triptorelin, 1 mg leuprolide and 10000 IU HCG were administered for final oocyte triggering in groups A (n = 63), B (n = 74) and C (n = 131), respectively. Demographic parameters were comparable between the groups. No cases of severe or moderate OHSS occurred in any group. The clinical pregnancy rates were 31.7%, 37.8% and 32.8% in groups A, B and C, respectively. Both injections had comparable efficacy in clinical outcome and OHSS risk. Regardless of preferred drug, GnRH agonist trigger for final oocyte maturation seems to be safe for patients with high OHSS risk, and can be safely used in fresh embryo transfer cycles.
卵巢功能較差者(取卵數量4-9顆者),胚胎全冷凍並無特別助益
原因可能在於子宮內膜受干擾程度較低

 2016 Nov 5. [Epub ahead of print]

Freeze-all cycle for all normal responders?

Abstract

PURPOSE:

The purpose of this study is to evaluate the freeze-all strategy in subgroups of normal responders, to assess whether this strategy is beneficial regardless of ovarian response, and to evaluate the possibility of implementing an individualized embryo transfer (iET) based on ovarian response.

METHODS:

This was an observational, cohort study performed in a private IVF center. A total of 938 IVF cycles were included in this study. The patients were submitted to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone (GnRH) antagonist protocol and a cleavage-stage day 3 embryo transfer. We performed a comparison of outcomes between the fresh embryo transfer (n = 523) and the freeze-all cycles (n = 415). The analysis was performed in two subgroups of patients based on the number of retrieved oocytes: Group 1 (4-9 oocytes) and Group 2 (10-15 oocytes).

RESULT(S):

In Group 1 (4-9 retrieved oocytes), the implantation rates (IR) were 17.9 and 20.5% (P = 0.259) in the fresh and freeze-all group, respectively; the ongoing pregnancy rates (OPR) were 31 and 33% (P = 0.577) in the fresh and freeze-all group, respectively. In Group 2 (10-15 oocytes), the IR were 22.1 and 30.1% (P = 0.028) and the OPR were 34 and 47% (P = 0.021) in the fresh and freeze-all groups, respectively.

CONCLUSION(S):

Although the freeze-all policy may be related to better in vitro fertilization (IVF) outcomes in normal responders, these potential advantages decrease with worsening ovarian response. Patients with poorer ovarian response do not benefit from the freeze-all strategy.

KEYWORDS:

Delayed frozen-t
服用抗乳癌藥tamoxifen後,卵巢功能(AMH, 基礎濾泡)並不會下降


 2016 Nov 22. pii: S0015-0282(16)62938-2. doi: 10.1016/j.fertnstert.2016.10.020. [Epub ahead of print]

Impact of tamoxifen therapy on fertility in breast cancer survivors.

Abstract

OBJECTIVE:

To determine whether tamoxifen use is associated with decreased ovarian reserve and decreased likelihood of having a child after a breast cancer diagnosis, using data from the Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women Study.

DESIGN:

Population-based cohort study.

SETTING:

Not applicable.

PATIENT(S):

Three hundred ninety-seven female breast cancer survivors aged 22-45 years whose cancer was diagnosed between ages 20 and 35 years and who were at least 2 years after diagnosis; 108 survivors also participated in a clinic visit.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Time to first child after cancer diagnosis, clinical measures of ovarian reserve (antimüllerian hormone [AMH] and antral follicle count [AFC]) after cancer.

RESULT(S):

Women who had ever used tamoxifen were substantially less likely to have a child after the breast cancer diagnosis (hazard ratio [HR] 0.29; 95% confidence interval [CI], 0.16, 0.54) than women who had never used tamoxifen. After adjusting for age at diagnosis, exposure to an alkylating agent, and race, the HR was 0.25 (95% CI, 0.14, 0.47). However, after adjusting for potential confounders, women who had used tamoxifen had an estimated geometric mean AMH level 2.47 times higher (95% CI, 1.08, 5.65) than women who had never taken tamoxifen. Antral follicle count was also higher in the tamoxifen group compared with the tamoxifen nonusers when adjusted for the same variables (risk ratio 1.21; 95% CI, 0.84, 1.73).

CONCLUSION(S):

Breast cancer survivors who had used tamoxifen were less likely to have a child after breast cancer diagnosis compared with survivors who never used tamoxifen. However, tamoxifen users did not have decreased ovarian reserve compared with the tamoxifen nonusers.

2016年11月28日

添加glycine 1mM於傳統玻璃化冷凍解凍液中,可提高鼠卵GV冷凍解凍存活率
添加glycine 1mM於傳統IVM培養液中,可提高鼠不成熟卵GV成熟率

 2016 Nov 15;6:37262. doi: 10.1038/srep37262.

Glycine increases preimplantation development of mouse oocytes following vitrification at the germinal vesicle stage.

Cao XY1,2Rose J3Wang SY1,2Liu Y4Zhao M1,2Xing MJ1,2Chang T1,2Xu B1,2.

Abstract

Ice-free cryopreservation, referred to as vitrification, is receiving increased attention in the human and animal assisted reproduction. However, it introduces the detrimental osmotic stress by adding and removing high contents of cryoprotectants. In this study, we evaluated the effects of normalizing cell volume regulation by adding glycine, an organic osmolyte, during vitrification of mouse germinal vesicle stage oocyte and/or subsequent maturation on its development. The data showed that glycine supplementation in either vitrification/thawing or maturation medium significantly improved the cytoplasmic maturation of MII oocytes manifested by spindle assembly, chromosomal alignment, mitochondrial distribution, euploidy rate, and blastocyst development following fertilization in vitro, compared to the control without glycine treatment. Furthermore, glycine addition during both vitrification/thawing and maturation further enhanced the oocyte quality demonstrated by various markers, including ATP contents and embryo development. Lastly, the effect of anti-apoptosis was also observed when glycine was added during vitrification. Our result suggests that reducing osmotic stress induced by vitrification could improve the development of vitrified mouse oocyte.

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2016年11月26日

目前建議儲存卵子以35歲前COH取卵二次,目標每次取15顆卵,儲存30顆卵子為宜

精蟲品質不佳濃度低於500萬,ICSI後胚胎染色體畸形率上升

嚴重稀少精蟲者ICSI後胚胎染色體畸形率大增(31%) (正常精蟲畸形率6%)

精蟲頭部空泡>50%頭部體積精蟲異常率大增

使用胚胎即時監測time lapse挑選胚胎可能可下降胚胎植入後之流產率(26>17%)

胚胎非整倍數染色體異常aneuploidy是胚胎流產之主要原因

AZF基因(AZFa, b, c)缺損是造成男性無精症之原因之一, 其中AZFc比AZFa, b更嚴重


file:///C:/Documents%20and%20Settings/xph/My%20Documents/Downloads/1183final.pdf

2016年11月24日

胚胎內部PH值約7.1-7.2
胚胎培養液PH值各種廠牌不一,平均約7.3 (7.2-7.4)

http://humupd.oxfordjournals.org/content/18/3/333.long

Is there an optimal pH for culture media used in clinical IVF?


Table III
Recommended pHe values for various commercial IVF media (adapted from Swain, 2010).
CompanyMediumRecommended pHe
CookSydney IVF Cleavage7.3–7.5
Sydney IVF Blastocyst7.3–7.5
Sydney IVF Fertilization7.3–7.5
FertiProFertiCult™ IVF7.2–7.6
FertiCult™ G37.3–7.6
GynemedGM501 Basic7.2–7.45
GM501 Cult7.2–7.45
InVitroCareIVC-ONE™7.25–7.45
IVC-TWO™7.25–7.45
IVC-THREE™7.25–7.45
IrvineP1®7.27–7.32
ECM®7.2–7.25
SSM™7.28–7.32
MultiBlast®7.3–7.4
HTF7.2–7.3
Life Globalglobal®7.2–7.4a
global® for Fertilization7.2–7.4a
Blastocyst7.2–7.4a
HTF7.2–7.4a
HTFxtra7.2–7.4a
OrigioUniversal IVF7.3–7.4
ISM1™7.2–7.3
ISM2™7.35–7.45
EmbryoAssist ™7.2–7.3
BlastAssist®7.35–7.45
EmbryoGen®7.2–7.3
SageQuinns Advantage® Fert7.3 ± 0.1
Quinns Advantage® Cleavage7.2 ± 0.1
Quinns Advantage® Blastocyst7.3 ± 0.1
VitrolifeG-IVF™ (G5-Series)7.35 ± 0.1
G-1™ (G5 Series)7.27 ± 0.07
G-2™ (G5 Series)7.27 ± 0.07
  • aCompany recommends 7.3.