三個正常染色體囊胚可提供93%的生育數率。

冷凍卵子時年齡小於35歲，平均需15個成熟卵細胞才能獲得三個正常染色體囊胚。

若患者年齡≥38歲，所成熟卵細胞數量增加一倍；，平均需30個成熟卵細胞才能獲得三個正常染色體囊胚。

若患者年齡≥40歲，則所需MII期卵母細胞數量增加至三倍，，平均需45個成熟卵細胞才能獲得三個正常染色體囊胚。。 

應鼓勵38歲之前進行卵子冷凍。

年齡≥38歲的女性，可能需要多次冷凍卵子週期才能獲得較高的活產率。

. 2025 Sep;124(3):487-495.

 doi: 10.1016/j.fertnstert.2025.04.023. Epub 2025 Apr 23.

The number of autologous, vitrified mature oocytes needed to obtain three euploid blastocysts increases with age

Objective: To determine the number of mature oocytes required to make at least three euploid blastocysts.

Subjects: All patients at a multicenter assisted reproductive technology practice that warmed vitrified autologous oocytes for in vitro fertilization from 2011 to October 2023.

Main outcome measures: Number of mature (metaphase II [MII]) oocytes to achieve at least three euploid blastocysts.

Results: A total of 1,041 thaw cycles from 986 patients were analyzed. Patients were stratified by age at vitrification. Measures of ovarian reserve decreased with advancing age, as expected. The number of mature oocytes (MII) banked and euploid blastocysts available decreased as age at vitrification increased. Patients aged 35-40 years used preimplantation genetic testing more than those older than 40 years or younger than 35 years. To optimize the chance of a potential live birth by banking at least three euploid blastocysts, patients aged <35 years at vitrification needed a mean of 15 MII oocytes. This number doubled in patients aged ≥38 years and tripled for patients aged >40 years. We also analyzed potential live birth per number of MII oocytes banked, which also increased with age, with 0.13 expected live births per thawed MII oocyte at the age of <35 years and 0.04 expected live births if older than 40 years at time of oocyte vitrification. Age at vitrification was more influential than indication for vitrification for expected outcome of live birth.

Conclusion: From previously published literature, three euploid blastocysts provided a 93% chance of a child. From our analysis, patients required a mean of 15 mature oocytes to yield at least three euploid blastocysts if they were aged <35 years at time of vitrification. The required number of MII oocytes doubled in patients aged ≥38 years and tripled in those aged ≥40 years, to achieve the same goal. Given our results, we should encourage egg freeze patients to cryopreserve before the age of 38 years. We should also counsel patients that multiple vitrification cycles will likely be required to achieve a high probability of live birth from future oocyte thaws for women aged ≥38 years.

PGT可能會下降累積活產率 尤其是<35歲患者

>40歲以上無明顯降低

J Assist Reprod Genet 2023 Jan;40(1):137-149.

 doi: 10.1007/s10815-022-02667-x. Epub 2022 Dec 1.

PGT-A is associated with reduced cumulative live birth rate in first reported IVF stimulation cycles age ≤ 40: an analysis of 133,494 autologous cycles reported to SART CORS

Purpose: To evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on cumulative live birth rate (CLBR) in IVF cycles.

Methods: Retrospective cohort study of the SART CORS database, comparing CLBR for patients using autologous oocytes, with or without PGT-A. The first reported autologous ovarian stimulation cycle per patient between January 1, 2014, and December 31, 2015, and all linked embryo transfer cycles between January 1, 2014, and December 31, 2016, were included in the study. Exclusion criteria were donor oocyte cycles, donor embryo cycles, gestational carrier cycles, cycles which included both a fresh embryo transfer (ET) combined with a thawed embryo previously frozen (ET plus FET), or cycles with a fresh ET after PGT-A.

Results: A total of 133,494 autologous IVF cycles were analyzed. Amongst patients who had blastocysts available for either ET or PGT-A, including those without transferrable embryos, decreased CLBR was noted in the PGT-A group at all ages, except ages > 40 (p < 0.01). A subgroup analysis of only those patients who had PGT-A and a subsequent FET, excluding those without transferrable embryos, demonstrated a very high CLBR, ranging from 71.2% at age < 35 to 50.2% at age > 42. Rates of multiple gestations, preterm birth, early pregnancy loss, and low birth weight were all greater in the non-PGT-A group.

Conclusions: PGT-A was associated with decreased CLBR amongst all patients who had blastocysts available for ET or PGT-A, except those aged > 40. The negative association of PGT-A use and CLBR per cycle start was especially pronounced at age < 35.

用 精子分離装置 (Zymot)。比傳統精蟲分離方式(DCC)可達到較高比率正常染色體囊胚

https://www.mdpi.com/2075-1729/15/2/302

採用 精子分離装置 (SSD)。比傳統精蟲分離方式可篩選出具有高活力且 DNA 損傷較少的精子群體，

. 2024 Aug;41(8):2201-2209.

 doi: 10.1007/s10815-024-03168-9. Epub 2024 Jun 18.

Optimized sperm selection: a highly efficient device for the isolation of progressive motile sperm with low DNA fragmentation index

Purpose: To identify the sperm preparation procedure that selects the best sperm population for medically assisted reproduction.Methods: Prospective observational study comparing the effect of four different sperm selection procedures on various semen parameters. Unused raw semen after routine diagnostic analysis was split in four fractions and processed by four different methods: (1) density gradient centrifugation (DGC), (2) sperm wash (SW), (3) DGC followed by magnetic activated cell sorting (MACS), and (4) using a sperm separation device (SSD). Each fraction was analyzed for progressive motility, morphology, acrosome index (AI), and DNA fragmentation index (DFI).Results: With DGC as standard of care in intraclass correlation coefficient analysis, only SSD was in strong disagreement regarding progressive motility and DFI [0.26, 95%CI (- 0.2, 0.58), and 0.17, 95%CI (- 0.19, 0.45), respectively]. When controlling for abstinence duration, DFI was significantly lower after both MACS and SSD compared to DGC [- 0.27%, 95%CI (- 0.47, - 0.06), p = 0.01, and - 0.6%, 95%CI (- 0.80, - 0.41), p < 0.001, respectively]. Further comparisons between SSD and MACS indicate significantly less apoptotic cells [Median (IQR) 4 (5), 95%CI (4.1, - 6.8) vs Median (IQR) 5 (8), 95%CI (4.9, - 9.2), p < 0.001, respectively] and dead cells [Median (IQR) 9.5 (23.3), 95%CI (13.2, - 22.4) vs Median (IQR) 22 (28), 95%CI (23.1, - 36.8), p < 0.001, respectively] in the SSD group.Conclusion: The selection of a population of highly motile spermatozoa with less damaged DNA from unprocessed semen is ideally performed with SSD. Question remains whether this method improves the embryological outcomes in the IVF laboratory.

Table 2.

Descriptive analysis of the effect of four different preparation techniques on concentration, progressive motility, normal morphology, AI, and DFI

	SW	DGC	MACS	SSD
Concentration (× 106)	61.7 ± 35.4 (17.5–193.0)	13.0 ± 11.6 (0.8–68)	8.4 ± 9.2 (0.61–49.6)	15.1 ± 14.2 (1.5–69.0)
Progressive motility (%)	54.3 ± 10.6 (23–86)	74.3 ± 11.8 (38–90)	77.2 ± 12.5 (37–92)	88.6 ± 4.2 (73–96)
Normal morphology (%)	3.3 ± 2.9 (0–13)	4.1 ± 3.1 (0–13)	4.2 ± 3.7 (0–18)	5.1 ± 3.9 (0–16)
AI (%)	8.5 ± 4.9 (1–20)	9.7 ± 6 (1–30)	8.7 ± 4.9 (0–19)	10.8 ± 6.8 (1–30)
DFI (%)	6.2 ± 4.6 (0.8–26.1)	2.7 ± 3.2 (0.2–14)	2.1 ± 4.3 (0.9–20.8)	0.2 ± 0.4 (0–2.3)

Fig. 2 

Capacity of MACS and SSD procedures to remove apoptotic (A) and dead (B) cells from sperm cell population (Wilcoxon signed-rank test). Spearman correlation test between the days of abstinence and the presence of dead cells in selected sperm population after MACS (C). Abbreviations: MACS: magnetic activated cell sorting, SSD: microfluidic sperm sorting

 未來可能niPGT 與傳統TE biopy 可能同時並用以防止TE biopsy偵測失敗

Review

 

. 2025 Oct 14;14(20):1591.

 doi: 10.3390/cells14201591.

Noninvasive Preimplantation Genetic Testing in Recurrent Pregnancy Loss and Implantation Failure: Breakthrough or Overpromise?

Background: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) are significant challenges in reproductive medicine. For both, embryonic aneuploidy is the leading etiological factor. Preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy is the current standard for embryo selection. However, it is limited by its invasiveness, potential for embryo damage, and diagnostic errors due to mosaicism. Rationale/Objectives: This review critically evaluates the emerging role of noninvasive PGT (niPGT). NiPGT analyzes cell-free DNA from spent blastocyst culture media, thus, it is a potential alternative for managing RPL and RIF. Hence, the primary objective is to determine whether current evidence supports niPGT as a reliable replacement for conventional biopsy-based PGT-A in these high-risk populations. Outcomes: The analysis reveals that niPGT offers significant theoretical advantages. These include complete non-invasiveness, enhanced embryo preservation, and high patient acceptability. However, its clinical application is hampered by substantial limitations. Key amongst them is the inconsistent and often suboptimal diagnostic accuracy (sensitivity 70-85%, specificity 88-92%) compared to biopsy. Other significant factors include the high rates of amplification failure (10-50%), vulnerability to maternal DNA contamination, as well as low DNA yield. Crucially, there is a definitive lack of robust, prospective randomized controlled trial (RCT) data demonstrating improved live birth rates or reduced miscarriage rates specifically in RPL and RIF cohorts. As such, niPGT is not yet ready to be a standalone clinical adoption in RPL and RIF cases. However, it may serve as a valuable adjunct for rescue scenarios following biopsy failure or for ethical reasons

niPGT vs. 傳統切片PGT----對應全染色體，染色體一致率仍有差距 (77 vs 91%)

Ploidy concordance rates in SBM-TE, SBM-WB, and TE-WB were 77.4% (130/168), 77.4% (130/168), and 90.5% (152/168),

Multicenter Study

 

. 2025 Oct;42(10):3479-3491.

 doi: 10.1007/s10815-025-03670-8. Epub 2025 Oct 7.

Validation of non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) in a Japanese population: experience from seven clinics

Purpose: The aim of this study was to determine the feasibility of implementing non-invasive PGT-A (niPGT-A) in clinical practice. Informativity and concordance rates between three sample types (embryonic cell-free DNA [cfDNA] present in spent blastocyst medium [SBM], trophectoderm [TE] biopsy, and whole blastocyst [WB]) from the same embryo were evaluated.

Methods: This was a prospective, multicenter study conducted between February 2022 and November 2022 at seven Japanese IVF centres. 212 blastocysts were donated for research. The cfDNA released into the SBM was analysed, and the results were compared against the corresponding TE biopsy and WB sample.

Results: Overall informativity rates for SBM, TE, and WB were 81.6% (173/212), 98.6% (209/212), and 98.6% (209/212), respectively. There was no difference between TE and WB; however, SBM was significantly different to both (p < 0.001). The informativity rate in SBM samples significantly varied among the seven centres, ranging between 72.7 and 97.1% (p = 0.041). Ploidy concordance (SBM-TE) also varied across the centres, ranging between 68.2 and 90.9%; however, this did not reach statistical significance (p = 0.63). Ploidy concordance rates in SBM-TE, SBM-WB, and TE-WB were 77.4% (130/168), 77.4% (130/168), and 90.5% (152/168), respectively. There was no statistical difference for SBM-TE and SBM-WB, but both were statistically different to TE-WB (p = 0.0054).

Conclusion: We have shown results that are consistent with the existing literature, indicating the feasibility of applying the niPGT-A protocol described here, and thus using the SBM result to establish a priority for embryo transfer.

 ni-PGT培養模式(微滴10-15uL, D4-6不更換培養液) 

----對囊胚無明顯不良影響

Observational Study

 

. 2024 Sep 1;39(9):1952-1959.

 doi: 10.1093/humrep/deae156.

The impact of implementing a non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) embryo culture protocol on embryo viability and clinical outcomes

Study question: Are modifications in the embryo culture protocol needed to perform non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) affecting clinical reproductive outcomes, including blastocyst development and pregnancy outcomes?

Summary answer: The implementation of an embryo culture protocol to accommodate niPGT-A has no impact on blastocyst viability or pregnancy outcomes.

What is known already: The recent identification of embryo cell-free (cf) DNA in spent blastocyst media has created the possibility of simplifying PGT-A. Concerns, however, have arisen at two levels. First, the representativeness of that cfDNA to the real ploidy status of the embryo. Second, the logistical changes that need to be implemented by the IVF laboratory when performing niPGT-A and their effect on reproductive outcomes. Concordance rates of niPGT-A to invasive PGT-A have gradually improved; however, the impact of culture protocol changes is not as well understood.

Study design, size, duration: As part of a trial examining concordance rates of niPGT-A versus invasive PGT-A, the IVF clinics implemented a specific niPGT-A embryo culture protocol. Briefly, this involved initial culture of fertilized oocytes following each laboratory standard routine up to Day 4. On Day 4, embryos were washed and cultured individually in 10 μl of fresh media. On Day 6 or 7, blastocysts were then biopsied, vitrified, and media collected for the niPGT-A analysis. Six IVF clinics from the previously mentioned trial were enrolled in this analysis. In the concordance trial, Clinic A cultured all embryos (97 cycles and 355 embryos) up to Day 6 or 7, whereas in the remaining clinics (B-F) (379 cycles), nearly a quarter of all the blastocysts (231/985: 23.5%) were biopsied on Day 5, with the remaining blastocysts following the niPGT-A protocol (754/985: 76.5%). During the same period (April 2018-December 2020), the IVF clinics also performed standard invasive PGT-A, which involved culture of embryos up to Days 5, 6, or 7 when blastocysts were biopsied and vitrified.

Essure 使用於輸卵管水腫可能造成IVF胚胎植入流產

輸卵管切除仍應優先考慮於此類病患

 Essure 是一種曾被廣泛使用的「永久性避孕裝置」，由拜耳（Bayer）公司開發。它是一對細小的金屬彈簧線圈（由鎳鈦合金、不鏽鋼及聚對苯二甲酸乙二酯纖維製成），透過陰道植入輸卵管中，誘發組織發炎並產生疤痕（纖維化），進而永久阻塞輸卵管以達到避孕效

High miscarriage rate in women treated with Essure® for hydrosalpinx before embryo transfer: a systematic review and meta-analysis

Essure® has been tested as an alternative treatment for hydrosalpinx before embryo transfer (ET) in women undergoing assisted reproduction techniques. However, the persistence of a foreign body inside the uterine cavity might have a negative impact on the outcome of pregnancy. The present systematic review aimed at identifying, appraising and summarizing the available evidence regarding the effectiveness and safety of using Essure prior to ET for women with hydrosalpinx.

Methods

We searched for studies in PubMed, Scopus, CENTRAL, Web of Science and ClinicalTrials.gov and the reference lists of eligible studies. All studies including at least 10 women with hydrosalpinx who received Essure, any other intervention or no treatment prior to ET were considered eligible. Study selection, data extraction and evaluation of the risk of bias were performed independently by two authors. Study outcomes were miscarriage per clinical pregnancy, singleton preterm birth per singleton live birth and live birth/ongoing pregnancy and clinical pregnancy per ET. The pooled results for each outcome and intervention were summarized as proportions with their respective 95% CIs, using a random-effects model.

Results

Our electronic search of databases was performed on 7 November 2015, and 26 studies with 43 study arms were considered eligible: eight study arms evaluating Essure; seven assessing tubal aspiration; seven appraising effects of no treatment; 12 evaluating salpingectomy; two assessing tubal division; and seven evaluating tubal occlusion. When compared with women who had no intervention, women with Essure had a higher clinical pregnancy rate per ET (36% (95% CI, 0–43%) vs 13% (95% CI, 9–17%)). When compared with women who had other interventions, women with Essure had a higher miscarriage rate per clinical pregnancy (38% (95% CI, 27–49%) vs 15% (95% CI, 10–19%)).

Conclusions

The available evidence suggests that, although Essure prior to ET in women with hydrosalpinx improves the chance of achieving a clinical pregnancy compared with no intervention, it is associated with a higher rate of miscarriage when compared with the other interventions. Although this evidence is based on observational studies, we believe that salpingectomy should be the first option for women who are eligible for videolaparoscopy. However, it is still premature to make recommendations for women who are not eligible for surgery, and randomized controlled trials are needed to clarify which is the best treatment alternative in such a scenario. 

 試管嬰兒罹患先天心臟病機率高於自然懷孕嬰兒 (1.30% vs 0.68%)

ltrasound in Obstetrics & Gynecology

Congenital heart defects in IVF/ICSI pregnancy: systematic review and meta-analysis

There is no consensus in current practice guidelines on whether conception by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) techniques is an indication for performing a fetal echocardiogram. The aim of the study was to assess whether congenital heart defects (CHD) occur more often in pregnancies conceived after IVF/ICSI as compared with those conceived spontaneously.

Methods

A systematic search for studies was conducted of PubMed/MEDLINE, EMBASE and Scopus from inception to September 2017. The search included the following medical subject heading (MeSH) terms alone or in different combinations: ‘IVF’, ‘IVF/ICSI’, ‘ART pregnancy’, ‘assisted conception’, ‘birth defect’, ‘congenital heart defects’ and ‘congenital malformation or abnormalities’. Studies comparing neonatal incidence of CHD in pregnancies conceived after IVF/ICSI and those conceived spontaneously were included. Studies reporting on other types of assisted reproductive technology (ART) or lacking information concerning termination of pregnancy were excluded. Chromosomal abnormalities were excluded in all analyzed studies. A meta-analysis of selected cohort studies was conducted to estimate the pooled odds ratio (OR) with 95% CI using a random-effects model. Statistical heterogeneity among the studies was evaluated with the I2 statistic and Q-test.

Results

Forty-one studies were identified for review including six case–control and 35 cohort studies. Data of eight selected cohort studies were used for meta-analysis. A total of 25 856 children conceived from IVF/ICSI techniques and 287 995 children conceived spontaneously, involving both singleton and multiple gestations, were included in the analysis. Total CHD events were 337/25 856 (1.30%) and 1952/287 995 (0.68%) in the IVF/ICSI and spontaneous conception groups, respectively. The risk of CHD was significantly increased in the IVF/ICSI group as compared with the spontaneous conception group (pooled OR, 1.45; 95% CI, 1.20–1.76; P = 0.0001; I2 = 44%; P = 0.08). In the subgroup of singleton IVF pregnancies, a significant difference was also obtained (OR, 1.55; 95% CI, 1.21–1.99; P = 0.0005; I2 = 36%; P = 0.18) and also multiple confounding factors adjusted ORs showed statistical significance (pooled OR, 1.29; 95% CI, 1.03–1.60; P = 0.02; I2 = 0%; P = 0.43).

Conclusion

Fetuses conceived with IVF/ICSI methods are at an increased risk of developing CHD compared with those conceived spontaneously. However, this finding deserves further investigation due to heterogeneity of both ART procedures and cardiac defects.  

在輔助生殖技術（ART）中，分開授精（Split Insemination） 主要指的是將取出的卵子分成兩組，分別使用不同的方法或精子來源進行受精。 

這種技術通常用於以下兩種主要情境：

1. 混合受精方式 (IVF + ICSI) 

這是最常見的臨床應用，又稱為「Half-ICSI」。實驗室會將同一批卵子（同胞卵子）隨機分成兩半： 

• 一組進行常規試管嬰兒 (IVF)： 讓精子與卵子在培養皿中自然結合。
• 另一組進行顯微注射 (ICSI)： 由胚胎師挑選單一精子直接注入卵子。 

主要目的：

• 防止受精失敗： 對於不明原因不孕或精子品質處於邊緣狀態（Borderline Semen）的夫婦，這能作為一種「保險」，確保至少有一組卵子能成功受精，避免整個週期無胚胎可用的窘境。
• 評估受精潛力： 觀察哪種方式效果更好，可作為未來治療週期的決策參考。
• 胚胎品質對比： 研究顯示，常規 IVF 產生的胚胎在某些情況下可能具有更好的囊胚發育潛能。