取卵數量達20顆以上應全數冷凍下周期再植入，以防卵巢過度刺激

J Ovarian Res. 2015 Nov 4;8:69. doi: 10.1186/s13048-015-0198-3.

A simplified universal approach to COH protocol for IVF: ultrashort flare GnRH-agonist/GnRH-antagonist protocol with tailored mode and timing of final follicular maturation.

Orvieto R1,2.

Author information

Abstract

Recently, several new promising modifications have been introduced to clinical practice that may simplify and optimize IVF outcome. In the present opinion paper we present a simplified approach to controlled ovarian hyperstimulation protocol (COH), which combines the benefits of the ultrashort flare GnRH agonist/GnRH antagonist protocol and the personalized tailored mode and timing of ovulation triggering, aiming to improve IVF outcome while eliminating of severe OHSS.In patients at risk to develop severe ovarian hyperstimulation syndrome (OHSS), GnRH agonist (GnRHa) trigger if offered for final follicular maturation. While in those achieving ≥20 oocytes, the freeze all policy with the subsequent frozen-thawed embryo transfers (ET) is recommended, in those where less than 20 oocytes are retrieved, patients are re-evaluated 3 days after oocyte retrieval (day of ET) for signs of early moderate OHSS. If no early signs of OHSS developed, one embryo was transferred, and the patients are instructed to inject 1500 IU of HCG. In cases where signs of early moderate OHSS appear, the freeze all policy is recommended.In Patients not at risk to develop severe OHSS- three different modes of concomitant administration of both GnRHa and a standard bolus of hCG (5000-10,000 units) prior to oocyte retrieval were suggested. Standard hCG dose concomitant with GnRHa (dual trigger), 35-37 h before oocyte retrieval is offered to normal responders patients, resulting in improved oocyte/embryo quality and IVF outcome. GnRHa 40 h and standard hCG added 34 h prior to oocyte retrieval (double trigger), respectively are offered to patients demonstrating abnormal final follicular maturation despite normal response to COH. The double trigger results in significantly higher number of oocytes retrieved, higher proportions of the number of oocytes retrieved to the number of follicles >10 mm and >14 mm in diameter on day of hCG administration, higher number of MII oocytes and proportion of MII oocytes per number of oocytes retrieved, with the consequent significantly increased number of top-quality embryos, as compared to the hCG-only trigger cycles. Standard hCG dose concomitant with GnRHa (dual trigger), 34 h before oocyte retrieval should be offered to poor responders patients, aiming to overcome premature luteinization, while achieving high yield of mature oocytes.Further studies are required to support this new concept prior to its implementation as a universal COH protocol to IVF practice.

冷凍卵巢組織切片大小: 5*5*2mm皮質組織(髓質組織無用)
冷凍用DMSO 解凍用EG可達較佳卵巢組織存活率

J Assist Reprod Genet. 2016 Oct 6. [Epub ahead of print]

Clinically applied procedures for human ovarian tissue cryopreservation result in different levels of efficacy and efficiency.

Bastings L1, Westphal JR1, Beerendonk CC1, Bekkers RL1, Zusterzeel PL1, Hendriks JC2, Braat DD1, Peek R3.

Author information

Abstract

PURPOSE:

Different protocols are being used worldwide for the cryopreservation of human ovarian tissue for fertility preservation purposes. The efficiency and efficacy of the majority of these protocols has not been extensively evaluated, possibly resulting in sub-optimally cryopreserved ovarian tissue. To address the impact of this issue, we assessed the effects of two clinically successful human ovarian tissue slow-freezing cryopreservation procedures on the quality of the cryopreserved tissue.

METHODS:

To differentiate between cryopreservation (C) versus thawing (T) related effects, four combinations of these two (A and B) very different cryopreservation/thawing protocols (ACAT, ACBT, BCAT, BCBT) were studied. Before and after cryopreservation and thawing, the percentage of living and morphologically normal follicles, as well as the overall tissue viability, was assessed.

RESULTS:

Our experiments revealed that the choice of the cryopreservation protocol noticeably affected the overall tissue viability and percentage of living follicles, with a higher viability after protocol BC when compared to AC. No statistically significant differences in tissue viability were observed between the two thawing protocols, but thawing protocol BT required considerably more human effort and materials than thawing protocol AT. Tissue morphology was best retained using the BCAT combination.

CONCLUSION:

Our results indicate that extensive and systematical evaluation of clinically used protocols is warranted.

冷凍卵巢組織移植後再施行IVF可達30%活產率

卵巢原始濾泡在移植後之減少並非全由於血管循環之受損，亦可能重新啟動原始卵子有絲分裂，干擾卵子細胞停滯之穩定狀況，造成原始卵子數量減少‧

J Assist Reprod Genet. 2016 Oct 8. [Epub ahead of print]

Ovarian tissue cryopreservation and transplantation: scientific implications.

Silber S1,2.

Author information

• 1Infertility Center of St. Louis, 224 South Woods Mill Road, Suite 730, Saint Louis, MO, 63017, USA. silber@infertile.com.
• 2Sun Yat-Sen Medical School, Guangzhou, China. silber@infertile.com.

Abstract

After fresh or frozen ovary transplantation, FSH levels return to normal, and menstrual cycles resume by 150 days, coincident with anti-Müllerian hormone rising to higher than normal levels. AMH then returns to well below normal levels by 240 days, remaining as such for many years with nonetheless normal ovulation and fertility. To date, 20 babies have been born in our program from 11 fresh and 13 cryopreserved ovary transplant recipients with a live baby rate of over 70 % (11 babies from fresh and 9 from frozen). Globally, over 70 live births have been reported for both fresh and frozen ovary transplants with an approximate 30 % live birth rate. Given the rapid rise of AMH after the fall of FSH, with a subsequent AMH decrease with retention of ovarian function, it is tempting to speculate the existence of a shared mechanism controlling primordial follicle recruitment, fetal oocyte meiotic arrest, and recruitment in the adult ovary. With the massive recruitment of primordial follicles observed after human ovarian cortical tissue transplantation, which subsides to an extremely low recruitment rate, we will discuss how this phenomenon suggests a unifying theory implicating ovarian cortical tissue rigidity in the regulation of both fetal oocyte arrest and recruitment of follicles in the adult ovary. As the paper by Winkler-Crepaz et al. in this issue demonstrates, our in vivo results are consistent with the in vitro demonstration that primordial follicles in the fetal cortex are "locked" in development, resulting in meiotic arrest, which spares the oocytes from being rapidly lost all at once (Winkler-Crepaz et al., J Assist Reprod Genet, 1). Winkler-Crepaz et al. demonstrate that follicle loss after ovarian cortex transplantation is unlikely due to ischemic apoptosis, but rather from a "burst" of primordial follicle recruitment. In vivo, primordial follicles are normally resistant to further development or activation to prevent oocyte depletion. The dense fibrous ovarian cortex, through as yet unresolved mechanisms, arrests the further continuation of meiosis and also prevents a sudden depletion of all resting follicles in the adult ovary. Intrinsic tissue pressure is released after cortical tissue transplantation, temporarily resulting in a rapid follicle depletion. These results are consistent with the observation that once the ovarian reserve is reduced in the graft, the rate of recruitment diminishes and the ovarian tissue exhibits a relatively long duration of function.

研究顯示，子宮外孕手術若保留輸卵管易造成日後再次發生子宮外孕

Hum Reprod. 2015 Sep;30(9):2038-47. doi: 10.1093/humrep/dev162. Epub 2015 Jul 13.

Cost-effectiveness of salpingotomy and salpingectomy in women with tubal pregnancy (a randomized controlled trial).

Mol F1, van Mello NM2, Strandell A3, Jurkovic D4, Ross JA5, Yalcinkaya TM6, Barnhart KT7, Verhoeve HR8, Graziosi GC9,Koks CA10, Mol BW11, Ankum WM2, van der Veen F12, Hajenius PJ2, van Wely M12; European Surgery in Ectopic Pregnancy (ESEP) study group.

Collaborators (26)

Author information

Abstract

STUDY QUESTION:

Is salpingotomy cost effective compared with salpingectomy in women with tubal pregnancy and a healthy contralateral tube?

SUMMARY ANSWER:

Salpingotomy is not cost effective over salpingectomy as a surgical procedure for tubal pregnancy, as its costs are higher without a better ongoing pregnancy rate while risks of persistent trophoblast are higher.

WHAT IS KNOWN ALREADY:

Women with a tubal pregnancy treated by salpingotomy or salpingectomy in the presence of a healthy contralateral tube have comparable ongoing pregnancy rates by natural conception. Salpingotomy bears the risk of persistent trophoblast necessitating additional medical or surgical treatment. Repeat ectopic pregnancy occurs slightly more often after salpingotomy compared with salpingectomy. Both consequences imply potentially higher costs after salpingotomy.

STUDY DESIGN, SIZE, DURATION:

We performed an economic evaluation of salpingotomy compared with salpingectomy in an international multicentre randomized controlled trial in women with a tubal pregnancy and a healthy contralateral tube. Between 24 September 2004 and 29 November 2011, women were allocated to salpingotomy (n = 215) or salpingectomy (n = 231). Fertility follow-up was done up to 36 months post-operatively.

PARTICIPANTS/MATERIALS, SETTINGS, METHODS:

We performed a cost-effectiveness analysis from a hospital perspective. We compared the direct medical costs of salpingotomy and salpingectomy until an ongoing pregnancy occurred by natural conception within a time horizon of 36 months. Direct medical costs included the surgical treatment of the initial tubal pregnancy, readmissions including reinterventions, treatment for persistent trophoblast and interventions for repeat ectopic pregnancy. The analysis was performed according to the intention-to-treat principle.

MAIN RESULTS AND THE ROLE OF CHANCE:

Mean direct medical costs per woman in the salpingotomy group and in the salpingectomy group were €3319 versus €2958, respectively, with a mean difference of €361 (95% confidence interval €217 to €515). Salpingotomy resulted in a marginally higher ongoing pregnancy rate by natural conception compared with salpingectomy leading to an incremental cost-effectiveness ratio €40 982 (95% confidence interval -€130 319 to €145 491) per ongoing pregnancy. Since salpingotomy resulted in more additional treatments for persistent trophoblast and interventions for repeat ectopic pregnancy, the incremental cost-effectiveness ratio was not informative.

電子顯微鏡顯示，不成熟卵子經體外培養(IVM)後，卵子內部胞器結構與一般成熟卵子無明顯差異

Mol Hum Reprod. 2016 Feb;22(2):110-8. doi: 10.1093/molehr/gav071. Epub 2015 Dec 7.

Ultrastructure of human oocytes after in vitro maturation.

Coticchio G1, Dal Canto M2, Fadini R2, Mignini Renzini M2, Guglielmo MC2, Miglietta S3, Palmerini MG4, Macchiarelli G4,Nottola SA3.

Author information

Abstract

STUDY HYPOTHESIS:

How does the ultrastructure of human oocytes matured in vitro compare with oocytes collected from women after full hormonal stimulation?

STUDY FINDING:

The ultrastructure of human oocytes matured in vitro is largely, but not entirely, similar to those matured in vivo.

WHAT IS KNOWN ALREADY:

Embryos derived from in vitro-matured oocytes often have limited developmental potential, possibly as an effect of inappropriate in vitro maturation (IVM) conditions. Transmission electron microscopy (TEM) is a valuable research tool to compare in vivo and in vitro matured oocytes. However, previous studies on the ultrastructure of human IVM oocytes were done with inadequate material or inappropriate IVM conditions, and have limited significance.

STUDY DESIGN, SAMPLES/MATERIALS, METHODS:

Immature cumulus cell-enclosed oocytes, retrieved from mid-sized antral follicles of women requiring IVM treatment, were matured in vitro for 30 h. No leftover germinal vesicle-stage oocytes collected from fully stimulated cycles were used. Control in vivo matured oocytes were obtained from age-matched women undergoing full ovarian stimulation. In vitro and in vivo matured oocytes were analysed by TEM and compared according to previously established morphometric criteria of oocyte quality.

MAIN RESULTS AND THE ROLE OF CHANCE:

All oocytes had normal ooplasm showing uniform distribution of organelles. Mitochondrial morphology appeared similar between the maturation conditions. Cortical granules were found typically stratified in a single, mostly continuous row just beneath the ooplasm in all oocytes. Microvilli were well preserved after IVM. Vacuoles were only occasionally found in all oocytes and, if present, they were frequently associated with lysosomes. Mitochondria-smooth endoplasmic reticulum (M-SER) aggregates and mitochondria-vesicles (MV) complexes were commonly found in in vivo matured oocytes. However, large MV complexes partially replaced M-SER aggregates in IVM oocytes.

使用GnRHa破卵該週期植入後黃體期需補充施打低劑量HCG以避免黃體期不足，懷孕率下降

J Assist Reprod Genet. 2016 Oct;33(10):1311-1318. Epub 2016 Jul 22.

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

Andersen CY1,2, Fischer R3, Giorgione V4, Kelsey TW5.

Author information

Abstract

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

動物實驗顯示，胚胎與脂肪細胞演化間質細胞共同培養
比傳統卵丘顆粒細胞共同培養更能提高胚胎之囊胚率&胚胎品質

J Assist Reprod Genet. 2016 Oct;33(10):1395-1403. Epub 2016 Jul 30.

Increasing of blastocyst rate and gene expression in co-culture of bovine embryos with adult adipose tissue-derived mesenchymal stem cells.

Miranda MS1,2, Nascimento HS3, Costa MP4, Costa NN3, Brito KN3, Lopes CT4, Santos SS3, Cordeiro MS3, Ohashi OM3.

Author information

Abstract

PURPOSE:

Despite advances in the composition of defined embryo culture media, co-culture with somatic cells is still used for bovine in vitro embryo production (IVEP) in many laboratories worldwide. Granulosa cells are most often used for this purpose, although recent work suggests that co-culture with stem cells of adult or embryonic origin or their derived biomaterials may improve mouse, cattle, and pig embryo development.

MATERIALS AND METHODS:

In experiment 1, in vitro produced bovine embryos were co-cultured in the presence of two concentrations of bovine adipose tissue-derived mesenchymal cells (b-ATMSCs; 103and 104 cells/mL), in b-ATMSC preconditioned medium (SOF-Cond), or SOF alone (control). In experiment 2, co-culture with 104 b-ATMSCs/mL was compared to the traditional granulosa cell co-culture system (Gran).

RESULTS:

In experiment 1, co-culture with 104 b-ATMSCs/mL improved blastocyst rates in comparison to conditioned and control media (p < 0.05). Despite that it did not show difference with 103 b-ATMSCs/mL (p = 0.051), group 104 b-ATMSCs/mL yielded higher results of blastocyst production. In experiment 2, when compared to group Gran, co-culture with 104 b-ATMSCs/mL improved not only blastocyst rates but also quality as assessed by increased total cell numbers and mRNA expression levels for POU5F1 and G6PDH (p < 0.05).

CONCLUSIONS:

Co-culture of bovine embryos with b-ATMSCs was more beneficial than the traditional co-culture system with granulosa cells. We speculate that the microenvironmental modulatory potential of MSCs, by means of soluble substances and exosome secretions, could be responsible for the positive effects observed. Further experiments must be done to evaluate if this beneficial effect in vitro also translates to an increase in offspring following embryo transfer. Moreover, this study provides an interesting platform to study the basic requirements during preimplantation embryo development, which, in turn, may aid the improvement of embryo culture protocols in bovine and other species.

分段式培養液 vs 單一培養液----臨床結果無差異

未來趨勢採單一培養液

J Assist Reprod Genet. 2016 Oct;33(10):1261-1272. Epub 2016 Aug 5.

Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials.

Sfontouris IA1,2, Martins WP3, Nastri CO3,4, Viana IG3,4, Navarro PA3, Raine-Fenning N1, van der Poel S5,6, Rienzi L7,Racowsky C8.

Author information

Abstract

PURPOSE:

The purpose of this study was to undertake a review of the available evidence comparing the use of a single medium versus sequential media for embryo culture to the blastocyst stage in clinical IVF.

METHODS:

We searched the Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials and WHO International Clinical Trials Registry Platform to identify randomized controlled trials comparing single versus sequential media for blastocyst culture and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or women. Eligible oocyte/zygote studies were analyzed to assess the risk difference (RD) and 95 % confidence intervals (CI) between the two media systems; eligible woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for clinical pregnancy rate.

RESULTS:

No differences were observed between single and sequential media for either ongoing pregnancy per randomized woman (relative risk (RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2 = 0 %) or clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 % CI = 0.4 to 4.3, two studies including 246 participants, I 2 = 0 %). Single media use was associated with an increase blastocyst formation per randomized oocyte/zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to +0.12, ten studies including 7455 oocytes/zygotes, I 2 = 83 %) but not top/high blastocyst formation (RD = +0.05, 95 % CI = -0.01 to +0.11, five studies including 3879 oocytes/zygotes, I 2 = 93 %). The overall quality of the evidence was very low for all these four outcomes.

CONCLUSIONS:

Although using a single medium for extended culture has some practical advantages and blastocyst formation rates appear to be higher, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of embryos to days 5/6. Future studies comparing these two media systems in well-designed trials should be performed.

分裂期胚胎內碎片(fragment) 是由粒腺體，高基氏體，lysosome組成( mitochondria-vesicle complexes, Golgi apparatus, primary lysosomes, and vacuoles)

移除碎片對胚胎懷孕率無明顯助益

J Assist Reprod Genet. 2016 Sep 10. [Epub ahead of print]

Ultrastructure of cytoplasmic fragments in human cleavage stage embryos.

Halvaei I1, Khalili MA2, Esfandiari N3, Safari S1, Talebi AR1, Miglietta S4, Nottola SA4.

Author information

Abstract

PURPOSE:

The goal of this study was to evaluate the ultrastructure of cytoplasmic fragments along with the effect of cytoplasmic fragment and perivitelline space coarse granulation removal (cosmetic microsurgery) from embryos before embryo transfer on ART outcomes.

METHODS:

One hundred and fifty intracytoplasmic sperm injection cycles with male factor infertility were included in this prospective study. Patients were divided into three groups of case (n = 50), sham (n = 50), and control (n = 50). Embryos with 10-50 % fragmentation were included in this study. Cosmetic microsurgery and zona assisted hatching were only performed in case and sham groups respectively. Extracted fragments were evaluated ultrastructurally by transmission electron microscopy (TEM). Rates of clinical pregnancy, live birth, miscarriage, multiple pregnancies, and congenital anomaly in the three groups were also compared.

RESULTS:

Micrographs from TEM showed that mitochondria were the most abundant structures found in the fragments along with mitochondria-vesicle complexes, Golgi apparatus, primary lysosomes, and vacuoles. There were no significant differences in demographic characteristics, laboratory and clinical data, or embryo morphological features between the groups. The rate of clinical pregnancy in control, sham, and case groups had no significant differences (24, 18, and 18 %, respectively). The rates of live birth, miscarriage, multiple pregnancy, and congenital anomaly were also similar between the different groups.

CONCLUSIONS:

Our data demonstrated that cosmetic microsurgery on preimplantation embryos had no beneficial effect on ART outcomes in unselected groups of patients. As mitochondria are the most abundant organelles found in cytoplasmic fragments, fragment removal should be performed with more caution in embryos with moderate fragmentation.

冷凍胚胎適應症:

卵巢過度刺激OHSS
P4>1.5
卵胚太少，品質不佳
內膜太薄, 積水
PGD
使用GnRHa (leuplin) 破卵


冷凍胚胎風險:
胚胎受損(10%左右)
胚胎品質越差，長的速度越慢，受損率越高


http://link.springer.com/article/10.1007%2Fs10815-016-0799-9

Table 2

Indications for frozen embryo transfers

FET indications
OHSS
Elevated progesterone
Genetic Screening
Low responders
Inadequate uterine cavity
Hypertension
Zika virus (areas affected)

Day3胚胎切片會延後胚胎形成桑葚體及囊胚之時間進而下降胚胎著床率

J Assist Reprod Genet. 2016 Oct 1. [Epub ahead of print]

Blastomere biopsy for PGD delays embryo compaction and blastulation: a time-lapse microscopic analysis.

Bar-El L1, Kalma Y1, Malcov M1, Schwartz T1, Raviv S1, Cohen T1, Amir H1, Cohen Y1, Reches A1, Amit A1, Ben-Yosef D2,3.

Author information

Abstract

PURPOSE:

The purpose of the study was to explore the effect of blastomere biopsy for preimplantation genetic diagnosis (PGD) on the embryos' dynamics, further cleavage, development, and implantation.

METHODS:

The study group included 366 embryos from all PGD treatments (September 2012 to June 2014) cultured in the EmbryoScope™ time-lapse monitoring system. The control group included all intracytoplasmic sperm injection (ICSI) embryos cultured in EmbryoScope™ until day 5 during the same time period (385 embryos). Time points of key embryonic events were analyzed with an EmbryoViewer™.

RESULTS:

Most (88 %) of the embryos were biopsied at ≥8 cells. These results summarize the further dynamic development of the largest cohort of biopsied embryos and demonstrate that blastomere biopsy of cleavage-stage embryos significantly delayed compaction and blastulation compared to the control non-biopsied embryos. This delay in preimplanation developmental events also affected postimplantation development as observed when the dynamics of non-implanted embryos (known implantation data (KID) negative) were compared to those of implanted embryos (KID positive).

CONCLUSION:

Analysis of morphokinetic parameters enabled us to explore how blastomere biopsy interferes with the dynamic sequence of developmental events. Our results show that biopsy delays the compaction and the blastulation of the embryos, leading to a decrease in implantation.

女性結紮病患施行試管若無明顯精蟲異常應優先採用IVF
IVF vs ICSI懷孕率無明顯差異

Hum Reprod. 2016 Oct 13. [Epub ahead of print]

Use of ICSI in IVF cycles in women with tubal ligation does not improve pregnancy or live birth rates.

Grimstad FW1, Nangia AK2, Luke B3, Stern JE4, Mak W5.

Author information

Abstract

STUDY QUESTION:

Does ICSI improve outcomes in ART cycles without male factor, specifically in couples with a history of tubal ligation as their infertility diagnosis?

SUMMARY ANSWER:

The use of ICSI showed no significant improvement in fertilization rate and resulted in lower pregnancy and live birth (LB) rates for women with the diagnosis of tubal ligation and no male factor.

WHAT IS KNOWN ALREADY:

Prior studies have suggested that ICSI use does not improve fertilization, pregnancy or LB rates in couples with non-male factor infertility. However, it is unknown whether couples with tubal ligation only diagnosis and therefore iatrogenic infertility could benefit from the use of ICSI during their ART cycles.

STUDY DESIGN, SIZE, DURATION:

Longitudinal cohort of nationally reported cycles in the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) of ART cycles performed in the USA between 2004 and 2012.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

There was a total of 8102 first autologous fresh ART cycles from women with the diagnosis of tubal ligation only and no reported male factor in the SART database. Of these, 957 were canceled cycles and were excluded from the final analysis. The remaining cycles were categorized by the use of conventional IVF (IVF, n = 3956 cycles) or ICSI (n = 3189 cycles). The odds of fertilization, clinical intrauterine gestation (CIG) and LB were calculated by logistic regression modeling, and the adjusted odds ratios (AORs) with 95% confidence intervals were calculated by adjusting for the confounders of year of treatment, maternal age, race and ethnicity, gravidity, number of oocytes retrieved, day of embryo transfer and number of embryos transferred.

MAIN RESULTS AND THE ROLE OF CHANCE:

The main outcome measures of the study were odds of fertilization (2PN/total oocytes), clinical intrauterine gestation (CIG/cycle) and live birth (LB/cycle). The fertilization rate was higher in the ICSI versus IVF group (57.5% vs 49.1%); however, after adjustment this trend was no longer significant (AOR 1.14, 0.97-1.35). Interestingly, both odds of CIG (AOR 0.78, 0.70-0.86), and odds of LB were lower (AOR 0.77, 0.69-0.85) in the ICSI group. Plurality at birth, mean length of gestation and birth weight did not differ between the two groups.

使用PGD偵測胚胎染色體正常植入仍然流產之原因在於部分胚胎之染色體呈現異常(31.6% were mosaic and 5.2% were polyploid )

結論: 目前傳統PGD aCGH偵測無法百分之百準確，偵測染色體正常仍有部分胚胎之染色體呈現異常(mosaicism, polyploid)

Fertil Steril. 2016 Sep 27. pii: S0015-0282(16)62686-9. doi: 10.1016/j.fertnstert.2016.08.017. [Epub ahead of print]

Why do euploid embryos miscarry? A case-control study comparing the rate of aneuploidy within presumed euploid embryos that resulted in miscarriage or live birth using next-generation sequencing.

Maxwell SM1, Colls P2, Hodes-Wertz B3, McCulloh DH3, McCaffrey C3, Wells D4, Munné S2, Grifo JA3.

Author information

Abstract

OBJECTIVE:

To determine whether undetected aneuploidy contributes to pregnancy loss after transfer of euploid embryos that have undergone array comparative genomic hybridization (aCGH).

DESIGN:

Case-control study.

SETTING:

University-based fertility center.

PATIENT(S):

Cases included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in miscarriage. Controls included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in a live birth.

INTERVENTION(S):

Next-generation sequencing (NGS) protocols were internally validated. Saved amplified DNA samples from the blastocyst trophectoderm biopsies previously diagnosed as euploid by aCGH were reanalyzed using NGS. Cytogenetic reports of the products of conception for 20 of the pregnancies resulting in miscarriage were available for comparison.

MAIN OUTCOME MEASURE(S):

The incidence of aneuploidy and mosaicism using NGS within embryos resulting in miscarriage and live birth.

RESULT(S):

Of euploid embryos analyzed by aCGH resulting in miscarriage, 31.6% were mosaic and 5.2% were polyploid by NGS. The rate of chromosomal abnormalities was significantly higher in embryos resulting in miscarriage (36.8%) than in those resulting in live births (15.8%). The rate of mosaicism was twice as high among embryos resulting in miscarriage than those resulting in live birth, but this was not statistically significant. Next-generation sequencing detected more cases of mosaicism than cytogenetic analysis of products of conception.

CONCLUSION(S):

Undetected aneuploidy may increase the risk of first trimester pregnancy loss. Next-generation sequencing may detect mosaicism and triploidy more frequently than aCGH, which could help to identify embryos at high risk of miscarriage. Mosaic embryos, however, should not be discarded as some can result in live births.