2015年11月8日

使用FSH+LH或使用HMG誘導排卵懷孕率類似

使用FSH+LH誘導排卵 vs 使用HMG誘導排卵

二者懷孕率類似

 2015 Jan;30(1):179-85. doi: 10.1093/humrep/deu302. Epub 2014 Nov 14.

Highly purified hMG versus recombinant FSH plus recombinant LH in intrauterine insemination cycles in women ≥35 years: a RCT.

Abstract

STUDY QUESTION:

Is the treatment with recombinant FSH (rFSH) plus recombinant LH (rLH) more effective than highly purified (HP)-hMG in terms of ongoing pregnancy rate (PR) in women ≥35 years of age undergoing intrauterine insemination (IUI) cycles?

SUMMARY ANSWER:

The ongoing PR was not significantly different in women treated with rFSH plus rLH or with HP-hMG.

WHAT IS KNOWN ALREADY:

Although previous studies have shown beneficial effects of the addition of LH activity to FSH, in terms of PR in patients aged over 34 years having ovulation induction, no studies have compared two different gonadotrophin preparations containing LH activity in women ≥35 years of age in IUI cycles.

STUDY DESIGN, SIZE, DURATION:

A single-centre RCT was performed between May 2012 and September 2013 with 579 women ≥35 years of age undergoing IUI cycles. The patients were randomly assigned to one of the two groups, rFSH in combination with rLH group or HP-hMG (Meropur) group, by giving them a code number from a computer generated randomization list, in order of enrolment. The randomization visit took place on the first day of ovarian stimulation.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Five hundred and seventy-nine patients with unexplained infertility or mild male factor undergoing IUI cycles were recruited in a university hospital setting. All women were enrolled in this study only for one cycle of treatment. Five hundred and seventy-nine cycles were included in the final analysis. Two hundred and ninety patients were treated with rFSH in combination with rLH and 289 patients were treated with HP-hMG. The ovarian stimulation cycle started on the third day of the menstrual cycle and the starting gonadotrophin doses used were 150 IU/day of rFSH plus 150 IU/day of rLH or 150 IU/day of HP-hMG. The drug dose was adjusted according to the individual follicular response. A single IUI per cycle was performed 34-36 h after hCG injection.

MAIN RESULTS AND THE ROLE OF CHANCE:

The main outcome measures were ongoing PR and number of interrupted cycles for high risk of ovarian hyperstimulation syndrome (OHSS). Ongoing pregnancy rates were 48/290 (17.3%) in the recombinant group versus 35/289 (12.2%) in the HP-hMG group [(odds ratio (OR) 1.50, 95% CI 0.94-2.41, P = 0.09]. The number of interrupted cycles for high risk of OHSS was 13/290 (4.5%) in the rFSH plus rLH group and 2/289 (0.7%) in the HP-hMG group (OR 6.73, 95% CI 1.51-30.12, P = 0.013).

自發性排卵反應隔一天即應施行人工受孕

自發性排卵反應隔一天即應施行人工受孕

隔2天施行人工受孕懷孕率會下降


 2014 Apr;29(4):697-703. doi: 10.1093/humrep/deu022. Epub 2014 Feb 18.

Should an intrauterine insemination with donor semen be performed 1 or 2 days after the spontaneous LH rise? A prospective RCT.

Abstract

STUDY QUESTION:

What is the impact on pregnancy rates when intrauterine insemination (IUI) is performed 1 or 2 days after the spontaneous LH rise?

SUMMARY ANSWER:

IUI 1 day after the spontaneous LH rise results in significantly higher clinical pregnancy rates compared with IUI performed 2 days after the LH rise.

WHAT IS KNOWN ALREADY:

IUI is scheduled within a limited time interval during which successful conception can be expected. Data about the optimal timing of IUI are based on inseminations following ovarian stimulation. There is no available evidence regarding the correct timing of IUI in a natural menstrual cycle following the occurrence of a spontaneous LH rise.

STUDY DESIGN, SIZE, DURATION:

A prospective RCT, including patients undergoing IUI with donor sperm in a natural menstrual cycle. IUI cycles (n = 435) were randomized between October 2010 and April 2013, of which 23 were excluded owing to protocol deviation and 412 received the allocated intervention.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Serial serum LH concentrations were analysed in samples taken between 07:00 and 09:00 h to detect an LH rise from Day 11 of the cycle onwards. The subjects were randomized to receive insemination either 1 or 2 days after the observed LH rise. In the final analysis, there were 213 cycles in the group receiving IUI 1 day after the LH rise and 199 cycles in the group receiving IUI 2 days after the LH rise.

MAIN RESULTS AND THE ROLE OF CHANCE:

Significantly higher clinical pregnancy rates per IUI cycle were observed in patients undergoing IUI 1 day after the LH rise when compared with patients undergoing IUI 2 days after the LH rise [19.7 (42/213) versus 11.1% (22/199), P = 0.02]. In view of the timing of sampling for LH, the inseminations were performed at 27 h (±2 h) and 51 h (±2 h) after detection of the LH rise. The risk ratio of achieving a clinical pregnancy if IUI was scheduled 1 day after the LH rise compared with 2 days was 1.78 [95% confidence interval (CI), 1.11-2.88]. This points towards a gain of one additional clinical pregnancy for every 12 cycles performed 1 day instead of 2 days after the LH rise. When analysing the results per patient, including only women who underwent their first treatment cycle of insemination, the outcome was in line with the per cycle analysis, demonstrating an 8% difference in pregnancy rate in favour of the early group (20.5 versus 12.2%), however, this difference was not significant.

2015年11月7日

施打hCG當天 P4/E2>0.35 ET後懷孕率會下降

施打hCG當天 P4>1.2或 P4/E2>0.35  ET後懷孕率會下降


 2015 Apr-Jun;8(2):80-5. doi: 10.4103/0974-1208.158606.

Do increased levels of progesterone and progesterone/estradiol ratio on the day of human chorionic gonadotropin affects pregnancy outcome in long agonist protocol in fresh in vitro fertilization/intracytoplasmic sperm injection cycles?

Abstract

BACKGROUND:

The effect of elevated levels of serum progesterone (P4) and estradiol (E2) on the day of human chorionic gonadotropin and their cut-off value on in vitro fertilization (IVF) outcomes is still not clear.

AIMS:

The aim was to evaluate the association between serum P4, E2 and progesterone/estradiol ratio (P4/E2) on pregnancy outcome in IVF/intracytoplasmic sperm injection (ICSI) cycles with long agonist protocol.

SETTING AND DESIGN:

Retrospective, single center, cohort study.

MATERIALS AND METHODS:

A review of complete data of 544 women undergoing fresh IVF/ICSI cycles (539 cycles) with long agonist protocol from January 2012 to February 2014 was done. Data were stratified into Three groups according to the number of oocytes retrieved: low (≤4 oocytes obtained), intermediate (5-19 oocytes obtained), and high ovarian response (≥20 oocytes obtained).

STATISTICAL ANALYSIS:

Fishers exact test/Chi-square was carried for comparing categorical data. Receiver operating characteristics analysis was performed to determine the cut-off value for P4 and P4/E2 detrimental for pregnancy.

RESULTS:

A negative association was observed between pregnancy rate (PR) and serum P4 and P4/E2 levels with no effect on fertilization and cleavage rate. The overall cut-off value of serum P4 and P4/E2 ratio detrimental for pregnancy was found to be 1.075 and ≥0.35, respectively. Different P4 threshold according to the ovarian responders were calculated, 1.075 for intermediate and 1.275 for high responders. Serum E2 levels were not found to be significantly associated with PR.

CONCLUSION:

Serum P4 levels and P4/E2 ratio are a significant predictor for pregnancy outcome without affecting cleavage and fertilization rate while serum estradiol levels do not seem to affect PR.

子宮內膜異位瘤手術處理不會明顯提高IVF懷孕率

子宮內膜異位瘤手術處理不會明顯提高IVF懷孕率


 2015 Nov;21(6):809-25. doi: 10.1093/humupd/dmv035. Epub 2015 Jul 12.

The impact of endometrioma on IVF/ICSI outcomes: a systematic review and meta-analysis.

Abstract

BACKGROUND:

Endometriosis is a disease known to be detrimental to fertility. Women with endometriosis, and the presence of endometrioma, may require artificial reproductive techniques (ART) to achieve a pregnancy. The specific impact of endometrioma alone and the impact of surgical intervention for endometrioma on the reproductive outcome of women undergoing IVF/ICSI are areas that require further clarification. The objectives of this review were as follows: (i) to determine the impact of endometrioma on IVF/ICSI outcomes, (ii) to determine the impact of surgery for endometrioma on IVF/ICSI outcome and (iii) to determine the effect of different surgical techniques on IVF/ICSI outcomes.

METHODS:

We performed a systematic review and meta-analysis examining subfertile women who have endometrioma and are undergoing IVF/ICSI, and who have or have not had any surgical management for endometrioma before IVF/ICSI. The primary outcome was live birth rate (LBR). Our secondary outcomes were clinical pregnancy rate (CPR), mean number of oocyte retrieved (MNOR), miscarriage rate (MR), fertilization rate, implantation rate, antral follicle count (AFC), total stimulating hormone dose, and any rates of adverse effects such as cancellation and associated complications during the IVF/ICSI treatment.

RESULTS:

We included 33 studies for the meta-analysis. The majority of the studies were retrospective (30/33), and three were RCTs. Compared with women with no endometrioma undergoing IVF/ICSI, women with endometrioma had a similar LBR (odds ratio [OR] 0.98; 95% CI [0.71, 1.36], 5 studies, 928 women, I(2) = 0%) and a similar CPR (OR 1.17; 95% CI [0.87, 1.58], 5 studies, 928 women, I(2) = 0%), a lower mean number of oocytes retrieved (SMD -0.23; 95% CI [-0.37, -0.10], 5 studies, 941 cycles, I(2) = 37%) and a higher cycle cancellation rate compared with those without the disease (OR 2.83; 95% CI [1.32, 6.06], 3 studies, 491 women, I(2) = 0%). Compared with women with no surgical treatment, women who had their endometrioma surgically treated before IVF/ICSI had a similar LBR (OR 0.90; 95% CI [0.63, 1.28], 5 studies, 655 women, I(2) = 32%), a similar CPR (OR 0.97; 95% CI [0.78, 1.20], 11 studies, 1512 women, I(2) = 0%) and a similar mean number of oocytes retrieved (SMD -0.17; 95% CI [-0.38, 0.05], 9 studies, 810 cycles, I(2) = 63%).

CONCLUSIONS:

Women with endometrioma undergoing IVF/ICSI had similar reproductive outcomes compared with those without the disease, although their cycle cancellation rate was significantly higher. Surgical treatment of endometrioma did not alter the outcome of IVF/ICSI treatment compared with those who did not receive surgical intervention. Considering that the reduced ovarian reserve may be attributed to the presence of endometrioma per se, and the potential detrimental impact from surgical intervention, individualization of care for women with endometrioma prior to IVF/ICSI may help optimize their IVF/ICSI results.

黃體期使用低劑量hCG可取代傳統黃體針補充療法

黃體期使用低劑量hCG (125iu/d)可取代傳統黃體針補充療法

http://www.ncbi.nlm.nih.gov/pubmed/26209535

 2015 Oct;30(10):2387-95. doi: 10.1093/humrep/dev184. Epub 2015 Jul 23.

Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone: a proof of concept trial.

Abstract

STUDY QUESTION:

Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care?

SUMMARY ANSWER:

Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support with exogenous progesterone.

WHAT IS KNOWN ALREADY:

A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase.

STUDY DESIGN, SIZE, DURATION:

This is a proof-of-concept study conducted as a three arm RCT with a total of 93 patients. First patient enrolled in January 2012 and the study finished in January 2014.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Normal responder women undergoing IVF/ICSI treatment in a university hospital. One arm served as control, where women followed a standard antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7.

MAIN RESULTS AND THE ROLE OF CHANCE:

The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid-luteal progesterone levels were significantly higher in the two study groups receiving daily low-dose hCG for luteal phase support as compared with the control group (control group: 177 ± 27 nmol/l; study group 1: 334 ± 42 nmol/l; study group 2: 277 ± 27 nmol/l; (mean ± SEM). No differences in reproductive outcome were seen between groups.

冷凍胚胎植入前不需誘導排卵即可達到類似懷孕率

冷凍胚胎植入前不需誘導排卵, 使用自然週期配合少量荷爾蒙藥劑即可達到類似懷孕率


 2015 Nov;30(11):2552-62. doi: 10.1093/humrep/dev224. Epub 2015 Sep 12.

Frozen-thawed embryo transfer in a natural or mildly hormonally stimulated cycle in women with regular ovulatory cycles: a RCT.

Abstract

STUDY QUESTION:

Can ovarian stimulation with low dose hMG improve the implantation rate (IR) per frozen-thawed embryo transferred (FET) when compared with natural cycle in an FET programme in women with a regular ovulatory cycle?

SUMMARY ANSWER:

Both IR and live birth rate (LBR) per FET were similar in the group with mild ovarian stimulation and the natural cycle group.

WHAT IS KNOWN ALREADY:

Different cycle regimens for endometrial preparation are used prior to FET: spontaneous ovulatory cycles, cycles with artificial endometrial preparation using estrogen and progesterone hormones, and cycles stimulated with gonadotrophins or clomiphene citrate. At present, it is not clear which regimen results in the highest IR or LBR. More specifically, there are no RCTs in ovulatory women comparing reproductive outcome after FET during a natural cycle and during a hormonally stimulated cycle.

STUDY DESIGN, SIZE, DURATION:

A total of 410 women scheduled for FET during 579 cycles (December 2003-September 2013) were enrolled in an open-label RCT to natural cycle (NC FET group, n = 291) or to a cycle hormonally stimulated with s.c. gonadotrophins (hMG FET group, 37.5-75 IU per day, n = 288). A total of 672 embryos were transferred during 434 cycles (332 embryos and 213 cycles in the NC FET group; 340 embryos and 221 cycles in the hMG FET group). Assuming a = 0.05 and 80% power, it was calculated that 219 frozen-thawed embryos were required for transfer in each group to demonstrate a difference of 10% in IR.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Women were eligible according to the following inclusion criteria: regular ovulatory cycle, female age ≥21 years and ≤45 years, informed consent. FET cycles with preimplantation genetic screening were excluded. The primary outcome was IR per embryo transferred. Secondary outcomes included IR with fetal heart beat (FHB), LBR per embryo transferred and endometrial thickness on the day of hCG administration. Statistical analysis was by intention to treat and controlled for the presence of multiple measures, as eligible women could be randomized in more than one cycle. Chi-square and independent t-test were used to compare categorical and continuous variables. The relative risk (RR) was estimated using a Poisson model with log link. Hierarchical models with random intercepts for patient and cycle were considered to account for clustering of cycles within patients and of embryos within cycles.

MAIN RESULTS AND THE ROLE OF CHANCE:

The primary outcome, IR per embryo transferred, was not statistically different between the NC FET group (41/332 (12.35%)) and in the hMG FET group (55/340 (16.18%)) (RR 1.3 (95% confidence interval (CI) 0.9-2.0), P = 0.19). Similarly, the secondary outcome, IR with FHB per embryo transferred, was 34/332 (10.24%) in the NC FET group and 48/340 (14.12%) in the hMG FET group (RR 1.4 (95% CI 0.9-2.1), P = 0.15). The LBR per embryo transferred was 32/332 (9.64%) in the NC FET group and 45/340 (13.24%) in the hMG FET group (RR 1.4 (95% CI 0.9-2.2), P = 0.17). Endometrial thickness was also similar in both groups [8.9 (95% CI 8.7-9.1) in the NC FET group and 8.9 (95% CI 8.7-9.1) in the hMG FET group]. The duration of the follicular phase was significantly shorter (P < 0.001) in the hMG FET group [13.7 days (95% CI 13.2-14.2)] than in the NC FET group [15.4 days (95% CI 14.8-15.9)].

LIMITATIONS, REASONS FOR CAUTION:

Randomization of cycles instead of patients; open-label design; relatively long period of recruitment.

WIDER IMPLICATIONS OF THE FINDINGS:

Our observation that the IR per embryo transferred is not significantly increased after FET during natural or gonadotrophin stimulated cycle, suggests that the effect of mild hormonal stimulation with gonadotrophins is smaller than what was considered clinically relevant with respect to reproductive outcome after FET. These data suggest that endometrial receptivity is not relevantly improved, but also not impaired after hormonal stimulation with gonadotrophins. Since FET during a natural cycle is cheaper and more patient-friendly, we recommend this regimen as the treatment of choice for women with regular cycles undergoing FET.

STUDY FUNDING/COMPETING INTERESTS:

The authors have no conflict of interest to declare. T.D. and K.P. were supported by the Clinical Research Foundation of UZ Leuven, Belgium. This study was also supported by the Ferring company (Copenhagen, Denmark), which provided free medication (Menopur) required for the group of patients who were randomized in the hMG FET group. The Ferring company was not involved in the study design, data analysis, writing and submission of the paper.

20-25%受孕卵子呈現染色體異常

IVF失敗主因為胚胎染色體異常
胚胎染色體異常主因為受孕過程減數分裂異常

20-25%受孕卵子呈現染色體異常

http://www.ncbi.nlm.nih.gov/pubmed/26255654

COH全程使用排卵藥D2~打破卵針可下降排卵針使用量

全程使用排卵藥clomid (D2~打破卵針)可下降排卵針使用量
卵子品質數量與受孕率並無減少
為避免clomid對子宮內膜之不良影響, 全數胚胎冷凍下週期再植入


 2015 Jul-Sep;8(3):142-5. doi: 10.4103/0974-1208.165151.

Clomiphene based ovarian stimulation in a commercial donor program.

Abstract

OBJECTIVE:

This study was conducted to compare an extended clomiphene-based ovarian stimulation regimen with the conventional antagonist protocol in donor-recipient cycles.

MATERIALS AND METHODS:

A total of 170 (N) donors were stimulated between January 2013 and December 2013. Conventional antagonist protocol (group I) was employed in (n1 = 31) cycles, and clomiphene was used in (n2 = 139) donor cycles (group II). 50 mg clomiphene was given simultaneously with gonadotropins from day 2 of the cycle until the day of trigger. The analysis was performed retrospectively for oocytes retrieved, fertilization rates, cycle cancelation, blastocyst formation, and pregnancy rates. The dosages, cost, and terminal E2 (estradiol) were also compared between the two groups.

RESULTS:

The donor age groups were comparable in both the groups. There were no unsuccessful egg retrievals with clomiphene. The pregnancy rate (positive beta human chorionic gonadotropin) was significantly higher in the clomiphene group (odds ratio: 2.453; P = 0.02). Similarly, fertilization rate was significantly higher in the clomiphene group (59.5/50.5, P = 0.04). Eggs retrieved were similar in both groups, but the terminal E2 was significantly higher in the clomiphene group (P = 0.001). Average gonadotropin used was also significantly lower in clomiphene group (P < 0.001).

CONCLUSION:

Clomiphene can effectively prevent luteinizing hormone surge and limit the dose of gonadotropins thus bringing down the costs and its negative impact on the endometrium and oocyte quality.

2015年10月30日

使用GnRHantagonis用於卵巢誘導破卵當期植入懷孕率&活產率較低

使用GnRHantagonist(腦下垂體拮抗劑)取代hCG用於卵巢誘導破卵

主要缺點: 當期植入(fresh ET)懷孕率&活產率較低

若改採冷凍胚胎下週期再植入懷孕率&活產率無明顯差異

2015年10月17日

陰道發炎感染可能跟懷孕早期流產有關

陰道發炎感染HPV, Chlamydia可能跟懷孕早期流產有關

陰道發炎感染者於胚胎植入前應治療其感染狀況


卵子冷凍保存時間不影響卵子品質

冷凍保存時間3年 vs 冷凍保存時間6年

解凍後卵子品質類似

子宮內膜較薄IVF後子宮外孕機率較高?

子宮內膜較薄IVF後子宮外孕機率較高?

6465懷孕研究顯示
IVF植入前內膜<9mm子宮外孕機率是
內膜>12mm子宮外孕機率的4倍


冷凍卵巢組織施行IVF懷孕率達3成

癌症病患接受卵巢組織冷凍保存

等癌症治療無復發疑慮後植入卵巢組織再施行試管懷孕率達3成


腦下垂體抑制劑無法有效保護化療或放射治療癌症病患之卵巢功能

傳統觀念認為腦下垂體抑制劑GnRHa可保護化療或放射治療癌症病患之卵巢功能

新研究顯示此觀念可能是錯誤


2015年10月10日

使用elonva誘導排卵始於第4天效果明顯低於始於第2天

使用elonva誘導排卵始於第2天效果類似始於第4天
卵子數量無明顯差異 (12.8 vs 14.7)

始於第2天使用排卵針劑量明顯高於始於第2天(324 vs 173 iu)


Elonva 150ug使用於高齡反應差病患,效果類似puregon每天450iu

Elonva 150ug 單一劑量, 使用於高齡反應差病患, 效果類似puregon 450iu/d x 7d


精蟲品質不佳之胚胎XY染色體異常機率明顯較高

精蟲品質不佳之病患施行試管嬰兒治療後胚胎XY染色體異常機率明顯高於一般精蟲品質正常之試管嬰兒病患


單一月經週期雙次誘倒排卵COH雙次取卵

單一月經週期雙次誘導排卵COH+雙次取卵
反應不佳卵數量較少之病患之另一增加卵數量之方法

使用止痛劑ketoprofen or indomethacin可用於抑制COH晚期自發性排卵

http://aspirecongress.org/wp-content/uploads/2014/02/How-to-do-Double-Stimulation-and-Egg-Recovery-for-Poor-Responders-Yanping-Kuang.pdf

http://www.ncbi.nlm.nih.gov/pubmed/24161646

卵子受孕方式會影響早期胚胎之分裂速度

卵子受孕方式(IVF vs ICSI)會影響早期胚胎之分裂速度
IVF速度慢於ICSI約1.5h

晚期胚胎影響較不明顯
可見晚期胚胎分裂速度主要取決於胚胎之品質

http://www.ncbi.nlm.nih.gov/pubmed/26307686

2015年10月3日

不明原因不孕症應常規施行子宮鏡檢查

不明原因不孕症之病患, 有高達20%具子宮內膜息肉
應常規施行子宮鏡檢查


囊胚內細胞體與染色體正常與否高度相關

囊胚期胚胎型態可預測其染色體正常與否

ICM(內細胞體)與染色體正常與否高度相關

異常ICM其囊胚染色體100%異常


2015年9月28日

多囊性卵巢與隱藏性糖尿病具相當程度關聯

高達36%之PCO(多囊性卵巢)印度女性呈現血糖耐受力異常
其中6%呈現明顯糖尿病

PCO 與隱藏性糖尿病具相當程度關聯

http://www.ncbi.nlm.nih.gov/pubmed/26407537

2015年9月12日

冷凍載具比較

冷凍載具比較
cryoloop 溫度速度遠大於其他載具

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660183/


An external file that holds a picture, illustration, etc.
Object name is 1477-7827-11-41-1.jpg
Comparison of the “closed” Rapid-i carrier to the “open” cryoloop. Diagram illustrates the two carriers, properties and compares cooling /warming rates.

Images in this article

8-cell比2-cell期胚胎具更高冷凍存活率

經玻璃化冷凍後, 8-cell期胚胎比2-cell期胚胎具更高存活率


試管懷孕流產8成原因為胚胎染色體異常

試管懷孕流產最常見原因為胚胎染色體異常(占82%)
尤其是胚胎染色體3套數之異常(占83%)
染色體最常見之異常為15,16,18,21,22染色體

 2015 Sep 7. pii: S0015-0282(15)01761-6. doi: 10.1016/j.fertnstert.2015.08.007. [Epub ahead of print]

Embryo selection versus natural selection: how do outcomes of comprehensive chromosome screening of blastocysts compare with the analysis of products of conception from early pregnancy loss (dilation and curettage) among an assisted reproductive technology population?

Abstract

OBJECTIVE:

To compare the incidence of numerical chromosomal abnormalities (NCAs) reported after preimplantation genetic screening (PGS) analysis compared with that reported after cytogenetic analysis of products of conception after spontaneous abortion.

DESIGN:

Retrospective study.

SETTING:

Private academic in vitro fertilization center.

PATIENT(S):

Cytogenetic reports of patients who underwent an IVF cycle with PGS of at least one biopsied embryo were compared with cytogenetic analysis reported from patients who had dilation and curettage (D&C) for the treatment of a spontaneous abortion after assisted reproductive technology (ART) treatment.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Frequencies for each numerical chromosomal abnormality from both groups were compared.

RESULT(S):

A total of 1,069 NCAs were reported after PGS (trisomy 54.3%, monosomy 45.7%, no polyploidies), resulting in a trisomy/monosomy ratio of 0.82. A total of 447 NCAs was reported after D&C (trisomy 83%, polyploidy 10.7%, monosomy 6.3%). The aneuploidies most frequently identified were similar in both groups and included 15, 16, 18, 21, and 22. Monosomies (n = 28, 6.3%) were rarely observed in the group that underwent D&C after ART.

CONCLUSION(S):

This review provides an analysis of the most commonly identified NCAs after PGS and in first-trimester D&C samples in an infertile population utilizing ART. Although monosomies comprised >50% of all cytogenetic anomalies identified after PGS, there were very few identified in the post-D&C samples. This suggests that although monosomies occur frequently in the IVF population, they commonly do not implant. Despite this difference, this study demonstrated that the specific NCAs observed after PGS analysis and D&C were comparable.

高齡病患卵針劑劑量450 vs 600 iu 懷孕率無明顯差異

針對高齡反應差poor responder之病患
高劑量誘導排卵針劑劑量450 iu vs 600 iu
懷孕率(16 vs18)&取卵數(4 vs 4)無明顯差異


 2015 Sep 7. pii: S0015-0282(15)01851-8. doi: 10.1016/j.fertnstert.2015.08.014. [Epub ahead of print]

450 IU versus 600 IU gonadotropin for controlled ovarian stimulation in poor responders: a randomized controlled trial.

Abstract

OBJECTIVE:

To compare the outcomes of controlled ovarian stimulation/in vitro fertilization cycles using 450 IU and 600 IU gonadotropin per day in women at risk of poor ovarian response.

DESIGN:

Prospective randomized controlled nonblinded study.

SETTING:

University-affiliated private IVF center.

PATIENT(S):

Women considered to be at risk of poor ovarian response: aged <41 years with basal FSH >10 IU/L, antimüllerian hormone <1 ng/mL, antral follicle count ≤8, or a previous IVF cycle with ≥300 IU/d gonadotropin that resulted in a cancellation, <8 follicles, or <5 oocytes.

INTERVENTION(S):

A total of 356 patients underwent a microdose GnRH agonist flare-up IVF/intracytoplasmic sperm injection protocol with a fixed daily dose of either 450 IU FSH (n = 176) or 600 IU FSH (n = 180) equally divided between Menopur and Bravelle.

MAIN OUTCOME MEASURE(S):

Number of mature oocytes retrieved.

RESULT(S):

The two groups were similar in terms of age, ovarian reserve, cause of infertility, duration of stimulation, and cycle cancellation rate. There were no significant differences in the number of metaphase II oocytes retrieved (4 [range 0-6] vs. 4 [range 2-7]), fertilization rate (62.4% vs. 57.0%), biochemical pregnancy rate (20.5% vs. 22.9%), clinical pregnancy rate (16.4% vs. 18.3%), and implantation rate (29.8% vs. 30.4%) between the 450 IU and 600 IU groups, respectively.

CONCLUSION(S):

Gonadotropin of 600 IU/d does not improve outcome of IVF cycles compared with 450 IU/d in women at risk of poor ovarian response.



2015年7月16日

排卵日前P4濃度過高會影響人工受孕IUI懷孕率

排卵日前1.5日之P4濃度過高>1.1會影響人工受孕IUI懷孕率

http://www.ncbi.nlm.nih.gov/pubmed/26171998

2015年7月4日

HCG使用於誘導排卵可能會干擾胚胎著床率

HCG (750iu/3d)使用於誘導排卵COH 期間,可能會干擾胚胎著床率

http://humrep.oxfordjournals.org/external-ref?access_num=19165663&link_type=MED

過早或過長使用hCG可能導致子宮內膜老化

COH過程中,過早或過長使用hCG,可能導致子宮內膜老化進而干擾胚胎著床

hCG會刺激卵巢黃體與子宮內膜之LH接受體,

http://humrep.oxfordjournals.org/content/28/6/1610.full


2015年6月24日

2015年6月13日

胚胎植入法Air fluid versus fluid-only懷孕率無明顯差異

胚胎植入法比較Air fluid versus fluid-only models
---懷孕率無明顯差異

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0025195/

P4過高超過2-3天懷孕率明顯下降

黃體素P4>1 超過1天懷孕率下降
黃體素P4>1 超過2-3天懷孕率明顯下降
卵泡越多,COH越長,P4>1 機率越高

http://humrep.oxfordjournals.org/content/27/7/2036.full

2015年6月10日

冷凍胚胎植入有較高懷孕率

冷凍胚胎植入vs 新鮮胚胎植入

冷凍胚胎植入有較高懷孕率

http://www.ncbi.nlm.nih.gov/pubmed/23040524

2015年6月9日

子宮內膜息肉占不明原因不孕症之比例高達20%

子宮內膜息肉占不明原因不孕症之比例高達16-26%
子宮內膜息肉占子宮內膜不孕症之比例高達46%

子宮內膜息肉小於2cm對IVF懷孕率影響較低

PCO病患應考慮減重以提高受孕率

http://humupd.oxfordjournals.org/content/17/2/242.full

2015年6月7日

不含glucose & phosphate 培養液有利胚胎生長分裂

不含glucose & phosphate 分裂期胚胎培養液(P1 Mediu, Irvine Scientific)
----仍達相同受孕率
----有利胚胎生長分裂

Composition of P1 Medium (Irvine Scientific)
NaHCO3  25 mM
Na-pyruvate 0.33 mM
Na-lactate 21.4 mM
Human serum 20%SSS is 1% albumin (hSA) equivalent to 1% hSA Amino acids
Taurine   0.05 mM
Na-citrate   0.15 mg/L

Phenol red   0.005 g/L

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455441/pdf/10815_2004_Article_494970.pdf

2015年6月6日

LH對於P4 level 無明顯影響

COH過程中補充LH對於P4 level 無明顯影響

hCG所含LH為rLH之7倍強

LH對P4形成及代謝影響相當複雜

http://humrep.oxfordjournals.org/content/27/1/232.full

2015年5月17日

hCG影響早期胎盤之發育

hCG影響早期懷孕(~8week)胎盤之發育


http://humrep.oxfordjournals.org/content/30/5/1029.abstract

2015年5月16日

施打hCG於COH末期,造成FSH & LH 下降

施打hCG於COH末期,造成FSH & LH 下降
施打hCG於COH末期, 懷孕率高於傳統COH(37  vs  29%)
施打hCG於COH末期, rFHS 劑量低於傳統COH(1273 vs 1617iu)

http://humrep.oxfordjournals.org/content/24/11/2910.full

化療前或化療中使用GnRHa可防止化療病患卵巢受損

化療前或化療中使用GnRHa可防止化療病患卵巢受損

不同化療藥劑對卵巢傷害不同(cyclophosphamide傷害>doxorubicin )
GnRHa對於不同化療藥劑之藥劑傷害之保護效果不同

http://humrep.oxfordjournals.org/content/30/5/1089.abstract

2015年5月13日

新一代玻璃化冷凍解凍液採用HPC及Trehalose

新一代玻璃化冷凍解凍液採用
hydroxypropyl cellulose (HPC)取代human origin albumin (HSA) (SSS)
Trehalose取代sucrose

http://highscope.ch.ntu.edu.tw/wordpress/?p=28317
https://clinicaltrials.gov/ct2/show/NCT01745523
http://cryotech-japan.jp/method/


2015年4月29日

男性不孕症之相關檢查

約有2000個基因與精蟲生長有關
其中只有30個基因位於Y染色體

http://www.jhrsonline.org/article.asp?issn=0974-1208;year=2013;volume=6;issue=3;spage=176;epage=182;aulast=Esteves

Spermatogenesis starts in adolescence and is controlled by genetic factors. It has been estimated that 2000 genes are essential for the full process to be completed; of these, only 30 genes are present in the Y chromosome. [12],[13]

男性不孕症之相關檢查

Table 1: Genetic tests in unexplained male infertility
Table 1: Genetic tests in unexplained male infertility

2015年4月27日

COH過程需考量2波FSH window

長療程可能優於短療程
pill+fixed GnRHantagonist可能優於flexible  GnRHantagonist

 we believe that stable and early suppression of endogenous gonadotrophins may be advantageous to achieve follicular synchronization and the highest clinical pregnancy rates. This may be achieved by either a long GnRH agonist protocol or a ‘long’ GnRH antagonist protocol (i.e. OC pretreated fixed GnRH antagonist protocol). In this respect, short or flexible regimens seem to be far from optimal. 

誘導排卵COH過程需考量2波FSH window




http://humrep.oxfordjournals.org/content/22/11/2805.full

2015年4月22日

IVF胚胎染色體正常比率

Day3前胚胎染色體正常率約30-35%
早期囊胚期染色體正常率約42%
成熟囊胚期染色體正常率約65%

2015年4月20日

2015年4月18日

GnRHantagonist 造成子宮內膜雌激素&黃體接受體表現下降

GnRHantagonist 造成子宮內膜雌激素ER alpha&黃體接受體PR表現下降

This study has shown that under the effect of a GnRH antagonist and rFSH with luteal phase progesterone supplementation, there is a significant down-regulation of PR in the surface epithelium. 


http://humrep.oxfordjournals.org/content/22/11/2981.full

2015年4月9日

clomid使用於誘導排卵會造成子宮內膜延後黃體化1-2天

FSH使用於誘導排卵會造成子宮內膜提早黃體化1-2天

clomid使用於誘導排卵會造成子宮內膜延後黃體化1-2天&子宮內膜變差
reduction of pinopod formation in the mid-luteal phase (Creus et al., 2003). 
The glandular density is reduced 

http://humupd.oxfordjournals.org/content/12/5/617.full

2015年4月6日

COH時間越長,可能造成子宮內膜老化, 進而降低懷孕率

COH時間越長, 延長濾泡期, 植入時間往後延後之結果,可能造成子宮內膜受E2刺激時間延長,造成子宮內膜老化,  進而降低懷孕率

http://humrep.oxfordjournals.org/content/21/4/1012.full

2015年4月5日

延後2天取卵可取較多卵子

傳統取卵時機為達3顆卵子>1.7cm
若不考慮內膜老化因素(轉為冷凍胚胎保存), 延後2天取卵可取較多卵子,

http://humrep.oxfordjournals.org/content/20/9/2453.full

http://www.ncbi.nlm.nih.gov/pubmed/15236997?dopt=Abstract

2015年3月28日

用hCG 200 iu 取代FSH於晚期誘導排卵

卵>1.2cm可以使用hCG 200 iu/d 取代FSH於誘導排卵

http://molehr.oxfordjournals.org/content/17/1/33.full

2015年3月26日

於取卵後D5-7施打3天GnRHantagonist可改善OHSS

於取卵後D5-7施打3天GnRHantagonist可改善卵巢過度刺激OHSS

OHSS造成血液濃稠, MCV>45, WBC>15000, 卵巢>10cm,


http://humrep.oxfordjournals.org/content/22/5/1348.full
http://humrep.oxfordjournals.org/content/28/7/1929.full

2015年3月13日

COH'劑量越高,施打hCG時P4越高

D2 hormone 標準值
FSH<10
LH<10
E2<60

COH'劑量越高,Day hCG時之E2越高 ,P4越高

P4高>1.5可能干擾胚胎著床

http://humrep.oxfordjournals.org/content/26/7/1813.full

2015年3月12日

P4大於1.5之機率約24%,懷孕率明顯較低

施打破卵針當天P4>1.5之機率約24%,

E2越高,COH劑量越高, 卵數量越多,P4>1.5之機率越高

P4>1.5懷孕率較低
P4>1.9懷孕率明顯較低

http://humrep.oxfordjournals.org/content/27/6/1822.full
http://humupd.oxfordjournals.org/content/19/5/433.full


2015年3月8日

PGD失敗錯誤率約10%

PGD基因放大偵測過程失敗錯誤率約10%
Genotype un-diagnosed28 (10%)
 Amplification failure14 (5%)
 Allele drop-out14 (5%)

http://humrep.oxfordjournals.org/content/28/5/1435.full

2015年1月24日

黃體期補充黃體素對於人工受孕無明顯助益

黃體期補充黃體素對於人工受孕無明顯助益(8.7%  vs 9.3%)

clomid 機轉
clomid抑制下視丘estrogen receptors進而增加GnRH分泌. 進而增加FSH & LH分泌
clomid可增加E2 & P4分泌

http://humrep.oxfordjournals.org/content/25/10/2501.full

2015年1月21日

使用排卵藥會抑制LH surge

使用排卵藥會抑制LH surge

http://molehr.oxfordjournals.org/content/19/12/799.full

精蟲穿入處若較靠近卵細胞原核處orPB處較易形成單一原核1PN

精蟲與卵子染色體亦可形成單一原核1PN

1PN原核有37%具有雙套染色體

精蟲穿入處若較靠近卵細胞原核處(or PB處)較易形成單一原核

http://www.biolreprod.org/content/52/3/653.abstract?ijkey=6b4531b439edea5e19aa14de3b08287eb7fe4e11&keytype2=tf_ipsecsha

2015年1月2日

單一原核及 3原核胚胎染色體分析


單一原核1PN or 3原核3PN

1PN 成因: 25%為孤雌生殖, 75%為PN形成時間點不一致asynchronous formation of pronuclei.
染色體分析

IVF後1PN培養後,48%胚胎染色體為雙套染色體
ICSI後1PN培養後,28%胚胎染色體為雙套染色體

IVF後3PN其染色體正常率為21%
ICSI後3PN其染色體正常率為13%
IVF後3PN其染色體misaicism比率較ICSI後3PNmisaicism比率為高

IVF後3PN胚胎分裂較正常胚胎為快
ICSI後3PN胚胎分裂較正常胚胎為慢

胚胎染色體異常應是胚胎著床失敗之主因

http://humrep.oxfordjournals.org/content/12/2/321.abstract?ijkey=3290be033de7b9d3f76573d38099f6c39b0a263b&keytype2=tf_ipsecsha


2014年12月21日

四分之一1PN會在20-24h post IVF形成2PN

16-18h post IVF觀察胚胎原核(PN), 單一原核胚胎1PN機率約 5%

4h後, 25%1PN會在20-22h post IVF形成2PN, 這些胚胎發展與正常胚胎無異

TimeLaps顯示60%胚胎之PN為一前一後asynchrony形成

1PN基因分析顯示單套染色體46%, 雙套染色體29%, mosaicism染色體25%

http://humrep.oxfordjournals.org/content/8/2/221.abstract?ijkey=ccb573e3a5f5208c360fe8c21c1ed238cf9da072&keytype2=tf_ipsecsha


2014年12月20日

1PN機轉

單一原核1PN胚胎
70%正常受孕但PN形成過程障礙或
30%孤雌生殖parthenogenetic

IVF較ICSI易形成1PN(2倍機率)

http://humrep.oxfordjournals.org/content/14/7/1869.long

hCG100-150iu誘導排卵可達不錯IVF懷孕率

IVF誘導排卵COH配合FSH+hCG100-150iu可達不錯懷孕率

http://humrep.oxfordjournals.org/content/27/10/3074.full


2014年12月6日

3PN胚胎可存活於4度達24h

3PN胚胎可存活於4度達24h

http://www.ncbi.nlm.nih.gov/pubmed/23820799

PCO濾泡會分泌較一般濾泡較高之AMH

多囊性卵巢PCO病患單一基礎濾泡會分泌較一般正常病患卵巢濾泡較高之AMH

http://www.fertstert.org/article/S0015-0282(14)02293-6/abstract

使用time-lapse 觀察胚胎分裂速度及型態可研判胚胎性別


使用胚胎即時監測系統time-lapse, 觀察胚胎分裂速度及型態可研判胚胎性別

http://www.fertstert.org/article/S0015-0282(14)02310-3/abstract


2014年11月11日

新一代自動化玻璃化冷凍胚胎與卵子儀器


Gavi 新一代自動化玻璃化冷凍儀器

Gavi - The World's First Automated Vitrification Instrument

冷凍胚胎與卵子臨床效果類似傳統cryotop玻璃化冷凍法


https://www.youtube.com/watch?v=EXcq77IGG2s

http://humrep.oxfordjournals.org/content/29/11/2431.abstract

2014年11月7日

IMSI對IVF懷孕結果無明顯助益

IMSI (傳高倍數挑選精蟲顯微注射)vs. ICSI(傳統精蟲顯微注射)

IMSI對IVF懷孕結果無明顯助益

http://www.ncbi.nlm.nih.gov/pubmed/23884963

2014年11月1日

Zona pellucida opening 優於ZP thinning

動物實驗顯示
中空透明帶Zona pellucida (ZP) opening可能優於ZP thinning

http://www.ncbi.nlm.nih.gov/pubmed/25267786