2015年12月27日

73例研究顯示, 人類囊胚具承受兩次切片兩次冷凍解凍PGD之能力
PGD若失敗可考慮解凍施行第2次PGD

 2014 Dec;102(6):1641-5. doi: 10.1016/j.fertnstert.2014.09.018. Epub 2014 Oct 22.

Blastocysts can be rebiopsied for preimplantation genetic diagnosis and screening.

Zhang S1Tan K2Gong F1Gu Y1Tan Y1Lu C1Luo K1Lu G3Lin G4.

Abstract

OBJECTIVE:

To evaluate the clinical value of re-examining the test-failure blastocysts in preimplantation genetic diagnosis/screening cycles.

DESIGN:

Retrospective study.

SETTING:

University-affiliated center.

PATIENT(S):

Women with test-failure blastocysts cryopreserved in preimplantation genetic diagnosis/screening cycles.

INTERVENTION(S):

Cryopreserved test-failure blastocysts were warmed and underwent a second round of biopsy, single nucleotide polymorphism microarray analysis, and vitrification, and the normal blastocysts were warmed again for ET.

MAIN OUTCOME MEASURE(S):

The percentage of test-failure blastocysts for transfer, the implantation rate per transferred blastocyst, and the live birth rate.

RESULT(S):

A total of 106 test-failure blastocysts from 77 cycles were warmed for re-examination. A total of 73 blastocysts that completely expanded were considered to have survived the warming process and were successfully rebiopsied. After single nucleotide polymorphism array analysis, 70 blastocysts yielded whole genome amplification product, and 31 had normal chromosomes (44.3%). A total of 19 normal blastocysts were warmed for ET, of which 18 survived and were transferred. The clinical pregnancy rate (implantation rate) was 50.0% in 10 single blastocyst transfer cycles, and all the implanted blastocysts resulted in healthy live births.

CONCLUSION(S):

Test-failure blastocysts that survived from the first warming procedure can tolerate a second round of biopsy, vitrification, and warming, have a high chance of having normal chromosomes, and are worth being re-examined.
7病歷顯示子宮移植1年後追蹤成效良好, 有規則月經, 充分血液供應, 可接受性之排斥現象

 2015 Jan;103(1):199-204. doi: 10.1016/j.fertnstert.2014.09.024. Epub 2014 Oct 22.

Uterus transplantation trial: 1-year outcome.

Abstract

OBJECTIVE:

To report the 12-month outcome of seven patients with viable uteri after uterus transplantation (UTx).

DESIGN:

Prospective observational study.

SETTING:

University hospital.

PATIENT(S):

Seven patients with absolute uterine infertility and viable uteri for 12 months after live-donor UTx.

INTERVENTION(S):

Predetermined immunosuppression was with tacrolimus and mychophenolate mofetil (MMF) during 6 months, whereupon MMF should be withdrawn. Frequent ultrasound examinations were performed to assess uterine appearance and uterine artery blood flow. Cervical biopsies (for histological detection of rejection) were obtained at preset time points, with temporary adjustments of immunosuppression if there were signs of rejection. Menstruations were systematically recorded.

MAIN OUTCOME MEASURE(S):

Menstruation, uterine artery blood flow, histology of cervical biopsies, and blood levels of tacrolimus.

RESULT(S):

All patients showed regular menses after 1-2 months. Uterine artery blood flow was unchanged, with a median pulsatility index of 1.9 (range, 0.5-5.4). Blood levels of tacrolimus were approximately 10, 9, and 8 (μg/L) during months 2, 9, and 12, respectively. Four recipients showed mild inflammation in biopsies after MMF withdrawal and were treated with corticosteroids and azathioprine during the remainder of the 12 months. Subclinical rejection episodes were detected on ectocervical biopsies in five recipients. Histology showed apoptotic bodies and occasional spongiosis in the squamous epithelium. Moderate infiltration of lymphocytes and neutrophils was seen in the epithelial/stromal interface. All rejection episodes were successfully treated for 2 weeks with corticosteroids or dose increments of tacrolimus.

CONCLUSION(S):

We demonstrate long-term uterine viability after UTx, with continued menstruation and unaltered uterine artery blood flow. Subclinical rejection episodes were effectively reversed by temporary increase of immunosuppression.

2015年12月26日

未來趨勢: 胚胎全數冷凍, 冷凍胚胎植入全部取代新鮮胚胎植入

 2015 May;103(5):1190-3. doi: 10.1016/j.fertnstert.2015.01.045. Epub 2015 Mar 4.

Freeze-all policy: fresh vs. frozen-thawed embryo transfer.

Abstract

OBJECTIVE:

To compare in vitro fertilization (IVF) outcomes between fresh embryo transfer (ET) and frozen-thawed ET (the "freeze-all" policy), with fresh ET performed only in cases without progesterone (P) elevation.

DESIGN:

Prospective, observational, cohort study.

SETTING:

Private IVF center.

PATIENT(S):

A total of 530 patients submitted to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone-antagonist protocol, and cleavage-stage, day-3 ET.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Ongoing pregnancy rates.

RESULT(S):

A total of 530 cycles were included in the analysis: 351 in the fresh ET group (when P levels were ≤1.5 ng/mL on the trigger day); and 179 cycles in the freeze-all group (ET performed after endometrial priming with estradiol valerate, at 6 mg/d, taken orally). For the fresh ET group vs. the freeze-all group, respectively, the implantation rate was 19.9% and 26.5%; clinical pregnancy rate was 35.9% and 46.4%; and ongoing pregnancy rate was 31.1% and 39.7%.

CONCLUSION(S):

The IVF outcomes were significantly better in the group using the freeze-all policy, compared with the group using fresh ET. These results suggest that even in a select group of patients that underwent fresh ET (P levels ≤1.5 ng/mL), endometrial receptivity may have been impaired by COS, and outcomes may be improved by using the freeze-all policy.
統計顯示冷凍胚胎植入懷孕可能較易胎盤黏連

 2015 May;103(5):1176-84.e2. doi: 10.1016/j.fertnstert.2015.01.021. Epub 2015 Mar 4.

Cryopreserved embryo transfer is an independent risk factor for placenta accreta.

Abstract

OBJECTIVE:

To explore the association between cryopreserved embryo transfer (CET) and risk of placenta accreta among patients utilizing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI).

DESIGN:

Case-control study.

SETTING:

Academic medical center.

PATIENT(S):

All patients using IVF and/or ICSI, with autologous or donor oocytes, undergoing fresh or cryopreserved transfer, who delivered a live-born fetus at ≥24 weeks of gestation at our center, from 2005 to 2011 (n = 1,571), were reviewed for placenta accreta at delivery.

INTERVENTION(S):

Cases of accreta (n = 50) were matched by age and prior cesarean section to controls (1:3) without accreta. The association between CET and accreta was modeled using conditional logistic regression, controlling a priori for age and placenta previa. Receiver operating characteristic curves were used to determine thresholds of endometrial thickness and peak serum E2 levels related to accreta.

MAIN OUTCOME MEASURE(S):

Placenta accreta.

RESULT(S):

Univariate predictors of accreta were non-Caucasian race (odds ratio [OR] 2.85, 95% confidence interval [CI] 1.25-6.47); uterine factor infertility (OR 5.80, 95% CI 2.49-13.50); prior abdominal or laparoscopic myomectomy (OR 7.24, 95% CI 1.92-27.28); and persistent or resolved placenta previa (OR 4.25, 95% CI 1.94-9.33). In multivariate analysis, we observed a significant association between CET and accreta (adjusted OR 3.20, 95% CI 1.14-9.02), which remained when analyses were restricted to cases of accreta with morbid complications (adjusted OR 3.87, 95% CI 1.08-13.81). Endometrial thickness and peak serum E2 level were each significantly lower in CET cycles and those with accreta.

CONCLUSION(S):

Cryopreserved ET is a strong independent risk factor for accreta among patients using IVF and/or ICSI. A threshold endometrial thickness and a "safety window" of optimal peak E2 level are proposed for external validation.
精蟲DNA碎片過多(>27.3%)會對高齡女姓ICSI懷孕結果產生不利影響

 2015 Apr;103(4):910-6. doi: 10.1016/j.fertnstert.2015.01.014. Epub 2015 Mar 4.

Effect of sperm DNA fragmentation on the clinical outcomes for in vitro fertilization and intracytoplasmic sperm injection in women with different ovarian reserves.

Jin J1Pan C1Fei Q1Ni W1Yang X1Zhang L1Huang X2.

Abstract

OBJECTIVE:

To investigate effect of sperm DNA fragmentation (SDF) on clinical outcomes of assisted reproductive technology in women with normal ovarian reserve (NOR) versus reduced ovarian reserve (ROR).

DESIGN:

Retrospective clinical study.

SETTING:

University-affiliated tertiary teaching hospital.

PATIENT(S):

A total of 2,865 consecutive couples undergoing their first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle.

INTERVENTION(S):

SDF assessed using sperm chromatin dispersion in sperm samples 1-2 months before treatment.

MAIN OUTCOME MEASURE(S):

SDF, IVF, and ICSI outcomes.

RESULT(S):

The grouping criteria were [1] basal follicle stimulating hormone >10 IU/L, [2] antral follicle count <6, and [3] female age ≥38 years. Women fulfilling two of the three criteria were considered to have ROR, and those not meeting any criteria were considered to have NOR. The area under the receiver operating characteristic curve was 0.594 (0.539-0.648) for the ROR group and 0.510 (0.491-0.530) for the NOR group. A cutoff value for SDF to predict the clinical pregnancy rate (CPR) in the ROR group was 27.3%. When the SDF exceeded 27.3%, the live-birth and implantation rates in the ROR group were statistically significantly decreased, but the clinical pregnancy, live-birth, and implantation rates were not affected in the NOR group. The risk of early abortion increased significantly in the NOR group when the SDF exceeded 27.3%.

CONCLUSION(S):

Sperm DNA fragmentation has a greater impact on IVF and ICSI outcomes among women with ROR, so SDF testing may be of particular clinical significance for these couples.



Each SCD assay was performed using the Halosperm kit (INDAS Laboratories) with a slight modification. In brief, the sperm concentration was diluted to 5–10 million per milliliter. The total volume was split into 30-μL aliquots on agarose gel in tubes that were placed in a water bath at 90–100°C for 5 minutes to fuse. The tubes were then placed in a water bath at 37°C for temperature equilibration. Next, 18 μL of the semen sample was added to each tube and mixed with the 30 μL of fused agarose, then 18 μL of the semen-agarose mixture was pipetted onto a precoated slide and covered with an 18 × 18-mm coverslip. The slide was placed in a refrigerator at 4°C for 5 minutes to allow the agarose to produce a microgel embedded with sperm cells. The coverslip was gently removed, and the slide was immediately immersed in an acid solution for 7 minutes. Next, the slide was immersed in lysing solution for 25 minutes. After 5 minutes of washing in a tray with abundant distilled water, the slide was dehydrated in increasing concentrations of ethanol (70%, 90%, and 100%) for 2 minutes each, and was then air dried.
For bright-field microscopy, each slide was covered with a mixture of Wright's staining solution and phosphate buffer solution (1:1) for 5–10 minutes. The slide was briefly washed in running water for 10 seconds and allowed to dry. Strong staining is preferred to achieve easy visualization of the periphery of the dispersed DNA loop halos. A minimum of 400 spermatozoa for each patient was scored according to the patterns established by Fernandez et al. (17). Sperm nuclei with fragmented DNA produce very small or no halos of dispersed DNA, whereas nuclei without DNA fragmentation release their DNA loops to form large halos. The percentage of sperm with very small or no halos was defined as the SDF level.
無中空透明帶(ZP)卵子仍可ICSI受孕, 培養至囊胚, 冷凍

 2015 May;103(5):e35. doi: 10.1016/j.fertnstert.2015.02.016. Epub 2015 Mar 13.

Time-lapse monitoring of zona pellucida-free embryos obtained through in vitro fertilization: a retrospective case series.

Abstract

OBJECTIVE:

To report time-lapse monitoring of human oocytes in which the damaged zona pellucida was removed, producing zona-free (ZF) oocytes that were cultured until the blastocyst stage in time-lapse incubators.

DESIGN:

Retrospective case series.

SETTING:

Private infertility clinic.

PATIENT(S):

Infertile patients (n = 32) undergoing minimal ovarian stimulation or natural cycle IVF treatment between October 2012 and June 2014.

INTERVENTION(S):

Intracytoplasmic sperm injection (ICSI) fertilization of ZF oocytes, prolonged embryo culture in time-lapse incubators, elective vitrification, and subsequent single vitrified-thawed blastocyst transfer (SVBT).

MAIN OUTCOME MEASURE(S):

Rate of fertilization, cleavage and blastocyst development, live-birth rate per SVBT cycle.

RESULT(S):

In spite of advanced maternal age (39 ± 4.2; range, 30-46 years), good fertilization (94%), cleavage (94%), and blastocyst development rates (38%) were reached after fertilization and culturing of ZF oocytes/embryos. All thawed ZF blastocysts survived, and up to this date seven SVBT transfers were performed, yielding three (43%) term live births with healthy newborns.

CONCLUSION(S):

Time-lapse imagery gives a unique insight into the dynamics of embryo development in ZF embryos. Moreover, our case series demonstrate that an oocyte with a damaged zona pellucida that has been removed could be successfully fertilized with ICSI, cultured until blastocyst stage in a time-lapse incubator and vitrified electively for subsequent use.
輸卵管受精 vs 傳統子宮受精
二者懷孕率無明顯差異

Fig 1
 2015 Jan-Mar;8(4):379-84. Epub 2015 Feb 7.

The comparison between Intrauterine Insemination and Fallopian Tube Sperm Perfusion Using FAST®System in Patients with Unexplained Infertility.

Abstract

BACKGROUND:

Controlled ovarian stimulation (COH) with intrauterine insemination (IUI) is commonly offered to infertile couples with patent fallopian tubes because it is simple, non-invasive and cost-effective technique. Another non-invasive method is fallopian tube sperm perfusion (FSP). This study was performed to compare the relative efficacy between FSP using fallopian sperm transfer (FAST) system and standard IUI in patients with unexplained infertility.

MATERIALS AND METHODS:

This prospective randomized study was conducted at the IVF Unit, Department of Gynecology and Obstetrics, Mazandaran University of Medical Sciences, Sari, Iran, from March 2011 to February 2012. A total of ninety patients with unexplained infertility underwent ovarian stimulation with clomiphene citrate and human menopausal gonadotropin (HMG). Patients were then randomly assigned into either group I (n=45) to undergo standard IUI or group II (n=45) to undergo FSP using FAST system.

RESULTS:

The patients' basic characteristics, including age, primary infertility and duration of infertility, were not significantly different between two study groups. In the group I, there were 9 pregnancies (a pregnancy rate per cycle of 20%), whereas in the group II, 8 pregnancies occurred (a pregnancy rate per cycle of 17.8%, p>0.05).

CONCLUSION:

FSP using FAST system offers no advantage over the standard IUI in order to increase pregnancy rate in patients with unexplained infertility.

2015年12月19日

卵細胞外圍之卵泡液&卵丘細胞對卵子成熟度與健全有關鍵影響

 2015 Feb;103(2):303-16. doi: 10.1016/j.fertnstert.2014.11.015. Epub 2014 Dec 10.

Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health.

Abstract

Bidirectional somatic cell-oocyte signaling is essential to create a changing intrafollicular microenvironment that controls primordial follicle growth into a cohort of growing follicles, from which one antral follicle is selected to ovulate a healthy oocyte. Such intercellular communications allow the oocyte to determine its own fate by influencing the intrafollicular microenvironment, which in turn provides the necessary cellular functions for oocyte developmental competence, which is defined as the ability of the oocyte to complete meiosis and undergo fertilization, embryogenesis, and term development. These coordinated somatic cell-oocyte interactions attempt to balance cellular metabolism with energy requirements during folliculogenesis, including changing energy utilization during meiotic resumption. If these cellular mechanisms are perturbed by metabolic disease and/or maternal aging, molecular damage of the oocyte can alter macromolecules, induce mitochondrial mutations, and reduce adenosine triphosphate production, all of which can harm the oocyte. Recent technologies are now exploring transcriptional, translational, and post-translational events within the human follicle with the goal of identifying biomarkers that reliably predict oocyte quality in the clinical setting.
男性健康狀況問題(心血管, 泌尿道, 內分泌)常合併精蟲品質不佳

 2015 Jan;103(1):66-71. doi: 10.1016/j.fertnstert.2014.10.017. Epub 2014 Dec 10.

Relationship between semen production and medical comorbidity.

Abstract

OBJECTIVE:

To study the relationship between semen quality and current health status in a cohort of men evaluated for infertility.

DESIGN:

Cross-sectional study.

SETTING:

Fertility clinic.

PATIENT(S):

Nine thousand three hundred eighty-seven men evaluated for infertility between 1994 and 2011.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Charlson comorbidity index, medical diagnoses by organ system.

RESULT(S):

At the time of evaluation, 9,387 men with a mean age of 38 years had semen data available. Of these men, 44% had at least one medical diagnosis unrelated to infertility. When stratifying the cohort by the Charlson comorbidity index (CCI), differences in all measured semen parameters were identified. Men with a higher CCI had lower semen volume, concentration, motility, total sperm count, and morphology scores. In addition, men with diseases of the endocrine, circulatory, genitourinary, and skin diseases all showed significantly higher rates of semen abnormalities. Upon closer examination of diseases of the circulatory system, men with hypertensive disease, peripheral vascular and cerebrovascular disease, and nonischemic heart disease all displayed higher rates of semen abnormalities.

CONCLUSION(S):

The current report identified a relationship between medical comorbidites and male semen production. Although genetics help guide a man's sperm production, his current condition and health play an important role.
罕見病例:  使用Letrozole (D3-7, 1# tid)懷孕6胞胎

 2015 Feb;103(2):535-6. doi: 10.1016/j.fertnstert.2014.10.040. Epub 2014 Dec 10.

First reported case of sextuplets conceived via letrozole for ovulation induction.

Abstract

OBJECTIVE:

To report the first case of sextuplets conceived via letrozole during ovulation induction.

DESIGN:

Case report.

SETTING:

Private fertility clinic.

PATIENT(S):

A 32-year-old female with a history of secondary infertility and polycystic ovary syndrome.

INTERVENTION(S):

Letrozole, 7.5 mg, on cycle days 3-7 after a progesterone-induced menses.

MAIN OUTCOME MEASURE(S):

Clinical pregnancy.

RESULT(S):

Sexchorionic-sexamniotic pregnancy.

CONCLUSION(S):

High-order multiple gestations are possible with letrozole ovulation induction, so patients should be counseled appropriately and follicle monitoring considered.
用微電泳分離精蟲
精蟲表面帶負電荷懷孕率較高, DNA受損較少

 2015 Feb;103(2):361-6.e3. doi: 10.1016/j.fertnstert.2014.10.047. Epub 2014 Dec 12.

Micro-electrophoresis: a noninvasive method of sperm selection based on membrane charge.

Abstract

OBJECTIVE:

To develop a technique with the potential of isolating genetically fit sperm for assisted reproductive technology (ART) treatment without compromising its structural or functional competence.

DESIGN:

Observational study.

SETTING:

University hospital.

PATIENT(S):

Fifty patients undergoing infertility diagnosis and 88 couples undergoing ART treatment.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Under an electric field, the percentage of positively charged sperm (PCS), negatively charged sperm (NCS), and neutrally charged sperm was determined for each ejaculate before and after density gradient centrifugation (DGC), and evaluated for sperm DNA damage, histone retention, and couples' ART outcomes. Subsequently, PCS, NCS, and neutrally charged sperm were selected using an intracytoplasmic sperm injection needle and directly analyzed for DNA damage.

RESULT(S):

There was a reduction in the NCS population (95.10% ± 0.94% vs. 54.48% ± 2.39%) and an increase in the PCS population (4.28% ± 0.58% vs. 42.52% ± 2.36%) after DGC. The DNA damage was inversely proportional to %NCS (r(2) = -0.242) and directly proportional to the %PCS (r(2) = 0.206). When sperm were picked according to their charge and directly analyzed, sperm DNA damage was lower in the NCS population (3.9% ± 1.5%) compared with control (17.3% ± 3.2%) and %PCS populations (27.8% ± 6.0%). The %NCS was positively associated with fertilization rate (r(2) = 0.469) and blastocyst development (r(2) = 0.308) and inversely associated with embryo arrest (r(2) = -0.253). Implantation rate and clinical pregnancies were higher in patient groups with increased NCS.

CONCLUSION(S):

Selection of NCS through micro-electrophoresis has the potential to isolate sperm relatively free of DNA damage to be used in ART.
50歲婦女用自己卵子試管懷孕生產
 2015 Feb;103(2):414-6. doi: 10.1016/j.fertnstert.2014.11.006. Epub 2014 Dec 13.

Live birth in a 50-year-old woman following in vitro fertilization-embryo transfer with autologous oocytes: a rare case report.

Abstract

OBJECTIVE:

To report a live birth with in vitro fertilization (IVF) from a 50-year-old woman with homologous oocytes.

DESIGN:

Case report.

SETTING:

Referral center.

PATIENT(S):

A 50-year-old woman.

INTERVENTION(S):

IVF with fresh embryo transfer (ET).

MAIN OUTCOME MEASURE(S):

Live birth after IVF.

RESULT(S):

A 50-year-old woman conceived with her own oocytes by means of IVF. Three fresh embryos were transferred, resulting in a pregnancy and delivery by cesarean section at 35 weeks of a healthy male baby weighing 2,300 g.

CONCLUSION(S):

Extensive literature search suggests that this is the first case report of live birth in a 50-year-old woman after IVF-ET with her own oocytes. This is a very rare and unusual case that deviates from the norm and therefore warrants attention. In selected cases, assisted reproductive technology might be reasonable to try for a limited number of times with a woman's own oocytes.
COH過程施打LH可能可下降P4上升之機率
LH/FSH比值<0.3-----P4上升之機率上升
LH/FSH比值>0.3-----P4上升之機率較低

 2014 Nov;102(5):1312-7. doi: 10.1016/j.fertnstert.2014.07.766. Epub 2014 Aug 20.

Defining the "sweet spot" for administered luteinizing hormone-to-follicle-stimulating hormone gonadotropin ratios during ovarian stimulation to protect against a clinically significant late follicular increase in progesterone: an analysis of 10,280 first in vitro fertilization cycles.

Abstract

OBJECTIVE:

To determine whether different ratios of administered LH-to-FSH influence the risk of clinically relevant late follicular P elevations and whether there is an optimal range of LH-to-FSH to mitigate this risk.

DESIGN:

Retrospective cohort.

SETTING:

Private academic center.

PATIENT(S):

A total of 10,280 patients undergoing their first IVF cycle.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

The ratio of exogenous LH-to-FSH throughout stimulation and association with absolute serum P level≥1.5 ng/mL on the day of hCG administration.

RESULT(S):

Stimulations using no administered LH (N=718) had the highest risk of P elevation≥1.5 ng/mL (relative risk [RR]=2.0; 95% confidence interval [CI] 1.8-2.2). The lowest risk of P increase occurred with an LH-to-FSH ratio of 0.30:0.60 (20%; N=4,732). In contrast, ratios<0.30, reflecting proportionally less administered LH (N=4,847) were at increased risk for premature P elevation (32%, RR=1.6; 95% CI 1.5-1.7) as were ratios>0.60 (23%, RR 1.1; 95% CI 1.0-1.3). This pattern of lowest risk in the 0.30-0.60 range held true for cycles characterized by low, normal, and high response. When performing a logistic regression to control for multiple confounding variables this relationship persisted.

CONCLUSION(S):

Absent or inadequate LH dosing is associated with a risk for a late follicular elevation in P sufficient to induce suboptimal outcomes. A total LH-to-FSH ratio of 0.30:0.60 was associated with the lowest risk of P elevation. Optimization of this parameter should be considered when making gonadotropin dosing decisions.