corifollitropin alfa (CFA) + intra-nasal GnRH agonist  (CFA flare)

VS

corifollitropin alfa (CFA) +GnRH antagonist

前者CFA flare方案是可取代傳統的卵巢刺激方案，用於治療卵巢反應不良的患者。

此方案顯著減輕了患者的負擔，減少了FSH注射次數，且無需注射GnRH拮抗劑。

CFA flare protocol is a novel alternative to conventional ovarian stimulation regimens that are used for ‘poor responder’ patients. It significantly reduces the patient burden, with less injections of FSH and no injections of GnRH antagonist. The ovarian response is similar to that achieved with a conventional GnRH antagonist cycle, 

An injection-lite approach to ovarian stimulation in poor responder patients using corifollitropin alfa and nasal GnRH agonist

Can the unique pharmacokinetic and pharmacodynamic profiles of corifollitropin alfa (CFA) in combination with an intra-nasal GnRH agonist (CFA flare) provide adequate ovarian stimulation for poor-responder patients while minimising the burden of injections?

Methods

Twenty women aged between 31 and 41 years of age who were identified as potential poor responders to ovarian stimulation according to the POSEIDON criteria and who were attending the Fertility and Research Centre, Royal Hospital for Women and City Fertility, Sydney for IVF treatment were randomised to receive either the flare or the antagonist cycle. Serum FSH, LH, and E2 concentrations were measured daily for 5 days post-initiation of CFA during the early follicular phase.

Results

The number of injections given to women in the CFA flare arm (4) was significantly less than those in the CFA antagonist arm (11), (p = 0.001).

Two days after the initiation of CFA, serum FSH concentrations were 27 versus 11 IU/L (flare versus antagonist) (p = 0.022), and mean serum E2 concentrations were 349 versus 157 pmol/L (p = 0.039), and on day 7, were 3000 versus 1850 pmol/L.

The CFA flare stimulation protocol resulted in higher concentrations of FSH in the early period of follicular stimulation. There was an equivalent rise in serum E2 in both groups. The CFA flare protocol was non-inferior to the CFA antagonist protocol and may have been less burdensome to patients as fewer injections were needed.

Conclusion

The CFA flare protocol is a novel alternative to conventional ovarian stimulation regimens that are used for ‘poor responder’ patients. It significantly reduces the patient burden, with less injections of FSH and no injections of GnRH antagonist. The ovarian response is similar to that achieved with a conventional GnRH antagonist cycle, but this requires further evaluation in a larger study.

用1 mM N-乙醯半胱氨酸（NAC）處理的卵母細胞與其他實驗組相比，卵裂率較高。

Oocytes treated with 1 mM N-acetylcysteine (NAC)  showed higher cleavage rates compared to the other experimental groups

Effect of in vitro maturation medium supplementation with N-acetylcysteine on the developmental competence of sheep oocytes

The present study aimed to evaluate the effect of N-acetylcysteine (NAC) on in vitro maturation (IVM) and in vitro embryo production in sheep. Cumulus–oocyte complexes (COCs) were collected and matured in vitro in a control medium or supplemented with different concentrations of NAC (1, 1.5 and 2.0 mM). After maturation, a subset of oocytes was used for morphological assessment and chromatin configuration analysis, as well as for evaluating intracellular levels of reactive oxygen species (ROS), glutathione (GSH), mitochondrial activity and DNA fragmentation using the TUNEL assay. Another subgroup of oocytes was subjected to in vitro fertilization (IVF), and the presumed zygotes were cultured in in vitro culture (IVC) medium to assess cleavage rates. Data were statistically analysed, considering significance at P < 0.05. The concentration of 1 mM NAC resulted in lower ROS levels compared to the control and 1.5 mM groups, in addition to reducing DNA fragmentation. No significant differences (P > 0.05) were observed in GSH levels or mitochondrial activity between treated and control groups. Furthermore, oocytes treated with 1 mM NAC showed higher cleavage rates compared to the other experimental groups. In conclusion, supplementation with 1 mM NAC improves oocyte quality and early embryonic development, as demonstrated by reduced oxidative stress and DNA fragmentation, resulting in increased cleavage rates.

• 嵌合體胚胎的著床率和活產率顯著低於整倍體胚胎，
• 一旦著床發生兩組的生化懷孕流失率和流產率相當，顯示著床是嵌合體胚胎存活的主要限制因素。
• 節段性嵌合體的預後優於全染色體嵌合體。

Meta-Analysis

 

. 2025 Aug;42(8):2469-2481.

doi: 10.1007/s10815-025-03575-6. Epub 2025 Jul 10.

Live birth and other reproductive outcomes of mosaic and euploid embryos: a systematic review and meta-analysis

Advances in preimplantation genetic testing for aneuploidy (PGT-A) have improved embryo selection in assisted reproductive technologies (ART). However, the clinical significance of mosaic embryos remains uncertain. This systematic review and meta-analysis evaluates reproductive outcomes following mosaic embryo transfer compared to euploid embryos. Live birth rate was the primary outcome, while secondary outcomes included biochemical pregnancy, biochemical pregnancy loss, miscarriage, clinical pregnancy, ongoing pregnancy, and neonatal outcomes. Our findings indicate that mosaic embryos have significantly lower implantation and live birth rates than euploid embryos, reinforcing the superior reproductive potential of euploid embryos. However, once implantation occurs, biochemical pregnancy loss and miscarriage rates were comparable between groups, suggesting that implantation is the primary limiting factor in mosaic embryo viability. The type and extent of mosaicism may further influence reproductive outcomes, with segmental mosaicism showing better prognoses than whole-chromosome mosaicism. Additionally, a trend toward lower birth weight in mosaic embryos was observed, though neonatal health outcomes remained as favorable as euploid embryos. The heterogeneity in diagnostic and reporting criteria highlights the need for standardized classification of mosaicism to enhance prognostic accuracy. Further research is required to refine embryo selection strategies and improve clinical decision-making in ART.

凍胚植入

Letrozole (LE)-induced ovulation vs hormone replacement treatment (HRT) 

----Letrozole誘導排卵可能可達到較高懷孕率

. 2025 May 8;42(6):1907–1915. doi: 10.1007/s10815-025-03500-x

Letrozole-stimulated cycles versus hormone replacement treatment cycles for frozen embryo transfer in women with polycystic ovary syndrome: a prospective randomized controlled trial

Purpose

This study aimed to compare the pregnancy outcomes of letrozole (LE)-induced ovulation and hormone replacement treatment (HRT) in endometrial preparation for frozen embryo transfer (FET) in women with polycystic ovary syndrome (PCOS).

Methods

A randomized controlled trial involved 200 patients with PCOS from December 2017 to December 2022. Participants, who underwent FET with one or two good-quality blastocysts or cleavage-stage embryos, were randomly assigned to the LE group or HRT group in a 1:1 ratio. The primary outcome was the clinical pregnancy rate. Secondary outcomes included biochemical pregnancy, implantation, ectopic pregnancy, miscarriage, multiple pregnancy, and live birth rates.

Results

The clinical pregnancy rate was 66.0% in the LE group compared to 53.0% in the HRT group (absolute difference, 13.0% [95% CI, − 0.5 to 26.5%]; RR, 1.25 [95% CI, 0.98 to 1.57]; P = 0.061). The biochemical pregnancy rate was higher in the LE group (71.0% vs 57.0%; absolute difference, 14.0% [95% CI, 0.8 to 27.2%]; RR, 1.25 [95% CI, 1.01 to 1.54]; P = 0.039). No significant differences were observed for the other secondary outcomes. The LE group showed higher biochemical pregnancy and live birth rates in the normal weight and normal androgen subgroups. Pregnancy outcomes were similar in the overweight and hyperandrogenic subgroups.

Conclusion

There were no statistically significant differences in clinical pregnancy rates between the LE and HRT cycles for FET in women with PCOS. However, the LE protocol may be a preferable option to HRT for women with normal weight or normal androgen levels. 

植入管內外管分批置入 vs 植入管內外管同時置入 

----先放外管再植入內管可達到較高懷孕率

 

Steps forward in embryo transfer technique: a retrospective study comparing direct versus afterload catheters at different time frames

Purpose

To assess whether embryo transfer (ET) technique can influence the clinical pregnancy rate (CPR) and its correlation with the embryo transfer difficulty.

Design

This single center retrospective cohort analysis of fresh and frozen single blastocyst transfers performed between January 2016 and December 2021 included fresh and frozen single blastocyst transfers performed during the study timeframe. Direct technique was the only one used from January 2016 to September 2017. From September 2017 to March 2019, the choice between the two techniques was given by randomization, due to a clinical trial recruitment. From April 2019, only the afterload technique was used. Preimplantation genetic testing cycles and gamete donation procedures and cycles performed with external gametes or embryos were excluded. CPR was the primary outcome, while difficult transfer rate the secondary one. Univariate and multivariate logistic regressions were performed.

Results

During the period, 8,189 transfers were performed. CPR of the afterload group resulted significantly higher compared to the direct group (44.69% versus 41.65%, OR 1.13, 95% CI 1.02–1.25, p = 0.017) and the rate of difficult transfers two-thirds lower (9.06% versus 26.85%, OR 0.27, 95% CI 0.24–0.31, p < 0.001).

Conclusion

Our study demonstrated that CPR is significantly affected by the ET technique. In particular, with the afterload protocol, both CPR and easy transfer rates increased.

 胚胎移植前子宮內注射 hCG 並不能提高活產率

Intrauterine human chorionic gonadotropin administration before embryo transfer (IHABT): an individual participant data meta-analysis of randomized controlled trials Open Access

Intrauterine administration of hCG has been considered as a promising IVF add-on before embryo transfer to improve fertility outcomes. A Cochrane review and four more recent systematic reviews all showed improved clinical pregnancy rates and/or live birth rates following intrauterine administration of hCG, however, a high unexplained heterogeneity was also present.

OBJECTIVE AND RATIONALE

To investigate the effectiveness and safety of intrauterine administration of hCG before embryo transfer in participants undergoing IVF. Individual participant data meta-analysis (IPD-MA) is recognized as the gold standard for evidence synthesis due to its ability to harmonize the data and to investigate treatment–covariate interactions. In addition, with recent experiences of guideline development and systematic review production raising increasing concerns about the trustworthiness of randomized controlled trials (RCTs) in women’s health research, an IPD-MA provides a unique opportunity to summarize the best available and most trustworthy evidence on this topic.

OUTCOMES

We detected 28 RCTs, of which 7 RCTs with IPD involving 2244 participants were included. All seven RCTs with IPD met trustworthiness criteria and six RCTs had overall low risk of bias. All RCTs without IPD did not meet trustworthiness criteria. IPD-MA showed intrauterine administration of hCG before embryo transfer did not improve live birth rates (7 RCTs, 2244 participants, odds ratio [OR] 0.99, 95% CI 0.83–1.19) or clinical pregnancy rates (7 RCTs, 2244 participants, OR 1.04, 95% CI 0.83–1.31). Studies without IPD showed different results from those with IPD for live birth (1.99, 0.72–5.50, P for interaction <0.001) and clinical pregnancy (1.87 (1.48–2.35), 17 RCTs without IPD, 3152 participants, P for interaction 0.005).

 10%PVP對於ICSI精子&卵子受孕成胚胎有不良影響

降低PVP濃度可能可改善

Concerns on use of PVP in assisted reproduction: a narrative review

The role of Polyvinylpyrrolidone (PVP) on human gametogenesis and embryonic development has been investigated in clinical setting. PVP is routinely used in sperm handling during intracytoplasmic sperm injection (ICSI) procedure. However, the controversies about its harmful effects on embryonic cells has been debated in recent years. Some reported that PVP decreases the membrane integrity and chromatin stability and strongly affects the fine structure of spermatozoa, such as axonemal tubules, fibrous sheath, and accessory fibres. However, others claimed that PVP delayed the onset of calcium oscillations in the oocyte in ICSI setting. Therefore, PVP affects the decondensation of male pronuclear formation after sperm injection. Also, it has been reported that after injection of conventional 10%PVP to embryos, PVP solution remained in the embryos and suppressed development of these embryos. Recent studies indicated that with a decrease in PVP concentration, embryo development increased and morphokinetics improved in ICSI cycles. Also, low concentration of PVP decreased the rate of apoptosis when compared to 10%PVP. In this review, the irreversible effects of PVP on sperm and embryonic chromosomal aberrant were reported. In conclusion, it is recommended to use the low concentration of PVP in conventional ICSI programme to limit its damage on fertilization processes as well as embryo development.

 卵泡<14mm 卵子成熟率只有40-50%

 卵泡<14mm 取出的比率只有60-80%

https://www.rbmojournal.com/article/S1472-6483(25)00253-6/fulltext

Follicular diameter	No. of cycles	Median oocyte retrieval rates (%)	95% CI
≥11 mm	429	60.0	54.3–65.7
≥12 mm	429	66.7	62.5–70.8
≥13 mm	429	72.7	68.0–77.4
≥14 mm	429	82.6	76.6–88.5
≥15 mm	429	100.0	92.1–107.9
≥16 mm	429	103.3	101.3–105.3
≥17 mm	426	133.3	123.3–143.4
≥18 mm	406	175.0	159.6–190.4
≥19 mm	374	250.0	225.3–274.7
≥20 mm	310	300.0	254.9–345.1
≥21 mm	229	333.3	268.8–397.9
≥22 mm	167	400.0	332.0–468.0
≥23 mm	101	400.0	304.4–495.6
≥24 mm	63	400.0	304.1–495.9

Table 2

Median oocyte retrieval rates

Median oocyte retrieval rates (95% CI) were measured by dividing the number of oocytes retrieved by the number of follicles measuring equal to or greater than each of the follicular diameters.

Bold type indicates statistical significance.

Follicular diameter	No. of cycles	Median mature oocyte retrieval rates (%)	95% CI
≥11 mm	218	42.9	39.4–46.3
≥12 mm	218	46.7	43.2–50.2
≥13 mm	218	50.0	46.1–53.9
≥14 mm	218	58.8	54.2–63.5
≥15 mm	218	66.7	62.1–71.2
≥16 mm	218	83.3	78.3–88.4
≥17 mm	216	100.0	90.9–109.1
≥18 mm	207	133.3	112.5–154.2
≥19 mm	188	200.0	176.4–223.6
≥20 mm	158	233.3	200.3–266.4
≥21 mm	117	300.0	228.1–371.9
≥22 mm	80	325.0	236.5–413.5
≥23 mm	47	300.0	235.3–364.7
≥24 mm	27	300.0	173.7–426.3

Table 3

Median mature oocyte retrieval rates

Median mature oocyte retrieval rates (95% CI) were measured by dividing the number of mature oocytes retrieved by the number of follicles measuring equal to or greater than each of the follicular diameters.

胚胎培養O2濃度

 5% O2濃度  vs  逐步下降 oxygen(8%–2%)濃度

-----5% O2濃度可得較高囊胚率&品質

Effect of constant (5%) versus gradient (8%–2%) oxygen concentration on sibling human blastocyst development

Research question

Does a gradient of oxygen concentration, decreasing from 8% to 2% during prolonged embryo culture, yield a higher percentage of morphologically optimal blastocysts compared with a static 5% oxygen atmosphere?

Design

This prospective sibling-split study included 658 cumulus-oocyte complexes from 44 intracytoplasmic sperm injection (ICSI) cycles (January 2022 to January 2023), alternately assigned to a control group (static 5% oxygen) or an intervention group (stepwise oxygen reduction: 8% on days 0-3, 5% on day 3, and 2% until days 5 or 6).

Results

Early embryo morphology was similar between groups. By day 5, following exposure to 2% oxygen from day 3, the control group produced a significantly higher proportion of clinically used blastocysts (47.3%, 122/258 vs. 36.9%, 97/263; P = 0.0161). Rates of morphologically optimal day-5 blastocysts were comparable (14.7%, 38/258 vs. 10.3%, 27/263; P = 0.2373). Time-lapse analysis showed delayed initiation of blastulation (P = 0.0024), blastocyst formation (P < 0.001), and expansion (P < 0.001) in the intervention group. Because of this delay, embryologists were more likely to select blastocysts for fresh transfer from the control group in a blinded procedure (P = 0.0088). Morphometric analysis showed significantly larger blastocyst cross-sectional area in the control group (28,198 ± 4139 vs. 25,994 ± 4657 µm2; P = 0.0014), consistent with more advanced expansion under constant 5% oxygen.

Conclusions

Gradually lowering oxygen from 8% to 2% during the second half of embryo culture resulted in delayed blastulation and fewer clinically used blastocysts when compared with culture under static 5% oxygen.

胚胎移植前子宮腔內注射人類絨毛膜促性腺激素（hCG）不太可能提高活產率或其他生育結果。

不論HCG施打劑量 時機 成分 凍胚或鮮胚等各種變因，均無明顯差異

dosage of hCG (500 IU vs ≥500 IU)

type of hCG (urinary hCG vs recombinant)

injection timing (on day of ET vs ≥2 days before ET)

transfer method (fresh vs frozen), 

Intrauterine human chorionic gonadotropin administration before embryo transfer (IHABT): an individual participant data meta-analysis of randomized controlled trials Open Access

Human Reproduction Update, dmag009, https://doi.org/10.1093/humupd/dmag009

Published:

 

16 April 2026 

Intrauterine administration of hCG before embryo transfer is unlikely to improve live birth rate or other fertility outcomes in individuals undergoing IVF, with low-moderate evidence available. We did not identify any patient subgroup that would benefit from the intervention. The differences between evidence from RCTs with and without IPD were likely due to major concerns about the trustworthiness of RCTs without IPD. Therefore, intrauterine hCG before embryo transfer should not be offered as an IVF add-on in clinical practice.

embryo transfer stage (cleavage vs blastocyst). s

使用波長為 498-563 nm 的綠色濾光片對胚胎發育率、形態品質或發育第 7 天和第 8 天的總細胞計數均無影響。

綠色濾光片對有害的藍光和紅外光具有保護作用。可降低壓力誘導型 Hsp72

綠色濾光片似乎可以降低體外受精 過程中光引起的刺激壓力‧

. 2009 Feb;24(2):308-14.

 doi: 10.1093/humrep/den432. Epub 2008 Dec 3.

Viability of bovine embryos following exposure to the green filtered or wider bandwidth light during in vitro embryo production

Background: Microscopic light during in vitro production (IVP) is a common stress factor compromising embryo development and viability. Many studies discussing detrimental effects of light have been conducted on in vivo matured/fertilized oocytes or on flushed embryos that were exposed to light only when cultured in vitro. The aim of this work was to examine the effects of light composition during all IVP steps on subsequent embryo development and quality. Methods: We compared the effects of a green pass filter of 498-563 nm wavelength, and a wider bandwidth of stereomicroscopic light on bovine embryo development rates, total cell counts and the presence of constitutive (Hsp73) and stress-inducible (Hsp72) forms of the Hsp70 protein. Results: The use of the green filter had no effect on embryo development rates, morphological quality or total cell counts on Day 7 or 8 of development compared with control group. However, Hsp72/73 protein levels revealed the protective effect of the filter against harmful blue and infrared regions of the light. The constitutive form Hsp73 was seen in both groups, but the inducible stress-response form Hsp72 was absent from the filter group embryos and appeared only in the group exposed to the stereomicroscopic light.

Conclusions: An easy to use and inexpensive green filter seems to reduce the stress caused by light during the IVP procedures without affecting either the accuracy of embryo monitoring or the need to increase the light intensity.