PGS盲點在於鑲嵌化胚胎，準確率(TE & whole blasotcyst cell 染色體一致)僅40%

Consistency between chromosomal status analysis of biopsied human blastocyst trophectoderm cells and whole blastocyst cells

Harunori Takahashi, Kazumasa Takahashi, Mayumi Goto, Takeo Hirakawa, Hisataka Hasegawa, Akihiro Shitara, Takuya Iwasawa, Kazue Togashi, Kenichi Makino, Hiromitsu Shirasawa … See all authors 

First published: 23 June 2021

 

https://doi.org/10.1002/rmb2.12400

Harunori Takahashi and Kazumasa Takahashi contributed equally as a first author.

Funding information:

This work was supported by JSPS KAKENHI (https://jsps.go.jp/english/index.html) (Grant Number 18H02942). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Purpose

This study investigated the consistency between results of preimplantation genetic testing for aneuploidy performed on trophectoderm (TE) cells and remaining blastocyst cells.

Methods

TE biopsy was performed on 29 surplus cryopreserved human blastocysts. Biopsy samples and remaining blastocysts were processed using the VeriSeq PGS kit, and chromosomal statuses were compared by next-generation sequencing.

Results

Discordance was observed in the chromosomal status of 11 out of 29 blastocysts between the biopsied TE and remaining blastocysts. Concordance was observed in 11 of 12 blastocysts classified as euploid by TE biopsy and in 7 of 17 blastocysts classified as aneuploid. There was 100% concordance (7/7) in cases diagnosed as aneuploid with no mosaicism by TE biopsy. However, discordance was observed in all 10 cases showing mosaicism or partial chromosomal abnormality.

Conclusion

Chromosomal status analysis based on TE biopsy does not accurately reflect the chromosomal status of the whole blastocyst. The chromosomal status is usually the same between the TE and remaining blastocyst cells in cases diagnosed as euploid or aneuploid with no mosaicism. However, mosaic blastocysts and those with other types of structural rearrangements have a higher risk of inconsistency, warranting caution during embryo selection.

使用捐贈新鮮卵子 vs 冷凍卵子  懷孕率並無差異

GnRH antagonist vs GnRHa vs progesterone 使用於LH suppression, PR無差異

Ovarian stimulation for oocyte donation: a systematic review and meta-analysis

Francisca Martinez, Annalisa Racca, Ignacio Rodríguez, Nikolaos P Polyzos

Human Reproduction Update, Volume 27, Issue 4, July-August 2021, Pages 673–696, https://doi.org/10.1093/humupd/dmab008

Published:

 

20 March 2021

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Abstract

BACKGROUND

Since its introduction in the 1980s, oocyte donation (OD) has been largely integrated into ART. Lately, both demand and the indications for OD have increased greatly. Oocyte donors are healthy and potentially fertile women undergoing voluntarily ovarian stimulation (OS). Selection of the optimal type of stimulation is of paramount importance in order to achieve the most favourable outcomes for the oocyte recipients, but most importantly for the safety of the oocyte donors.

OBJECTIVE AND RATIONALE

This is the first systematic review (SR) with the objective to summarize the current evidence on OS in oocyte donors. The scope of this SR was to evaluate the OD programme by assessing four different aspects: how to assess the ovarian response prior to stimulation; how to plan the OS (gonadotrophins; LH suppression; ovulation trigger; when to start OS); how to control for the risk of ovarian hyperstimulation syndrome (OHSS) and other complications; and the differences between the use of fresh versus vitrified donated oocytes.

SEARCH METHODS

A systematic literature search was conducted in May 2020, according to PRISMA guidelines in the databases PubMed and Embase, using a string that combined synonyms for oocytes, donation, banking, freezing, complications and reproductive outcomes. Studies reporting on the safety and/or efficacy of OS in oocyte donors were identified. The quality of the included studies was assessed using ROBINS-I and ROB2. Meta-analysis was performed where appropriate. Data were combined to calculate mean differences (MD) for continuous variables and odd ratios (OR) for binary data with their corresponding 95% CIs. Heterogeneity between the included studies was assessed using I2 and tau statistics.

OUTCOMES

In total, 57 manuscripts were selected for the review, out of 191 citations identified. Antral follicle count and anti-Müllerian hormone levels correlate with ovarian response to OS in OD but have limited value to discriminate donors who are likely to show either impaired or excessive response. Five randomized controlled trials compared different type of gonadotrophins as part of OS in oocyte donors; owing to high heterogeneity, meta-analysis was precluded. When comparing different types of LH control, namely GnRH antagonist versus agonist, the studies showed no differences in ovarian response. Use of progesterone primed ovarian stimulation protocols has been evaluated in seven studies: the evidence has shown little or no difference, compared to GnRH antagonist protocols, in mean number of retrieved oocytes (MD 0.23, [95% CI 0.58–1.05], n = 2147; 6 studies; I2 = 13%, P = 0.33) and in clinical pregnancy rates among recipients (OR 0.87 [95% CI 0.60–1.26], n = 2260, I2 = 72%, P < 0.01). There is insufficient evidence on long-term safety for babies born. GnRH agonist triggering is the gold standard and should be used in all oocyte donors, given the excellent oocyte retrieval rates, the practical elimination of OHSS and no differences in pregnancy rates in recipients (four studies, OR 0.86, 95%CI 0.58–1.26; I2 = 0%). OS in OD is a safe procedure with a low rate of hospitalization after oocyte retrieval. The use of a levonorgestrel intrauterine device or a progestin contraceptive pill during OS does not impact the number of oocytes retrieved or the clinical pregnancy rate in recipients. Ultrasound monitoring seems enough for an adequate follow up of the stimulation cycle in OD. Use of fresh versus vitrified donated oocytes yielded similar pregnancy outcomes.

 凍胚植入FET，該週期雖為自然周期，仍需補充黃體素 & hCG以提升懷孕率

Should women receive luteal support following natural cycle frozen embryo transfer? A systematic review and meta-analysis

Yossi Mizrachi, Eran Horowitz, Hadas Ganer Herman, Jacob Farhi, Arieh Raziel, Ariel Weissman

Human Reproduction Update, Volume 27, Issue 4, July-August 2021, Pages 643–650, https://doi.org/10.1093/humupd/dmab011

Published:

 

08 April 2021

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Abstract

BACKGROUND

Spontaneous ovulation during a natural menstrual cycle is frequently used for timing frozen embryo transfer (FET). Nevertheless, it remains unclear whether or not women should receive luteal phase support (LPS) following natural cycle frozen embryo transfer (NC-FET).

OBJECTIVE AND RATIONALE

The aim of this systematic review and meta-analysis was to study whether the administration of LPS improves the reproductive outcome following NC-FET.

SEARCH METHODS

We conducted a systematic search of the literature published in Medline/PubMed, Embase and the Cochrane Library, from January 2000 until December 2020. We included all original English, peer-reviewed articles, irrespective of the study design. The search strategy included keywords related to NC-FET and luteal phase support. Studies reporting the results of artificial or stimulated FET cycles were excluded.

OUTCOMES

Our systematic search generated 416 records. After screening, eight studies were included in the review and seven studies were included in the meta-analysis. Two studies (n = 858) used hCG and six studies (n = 1507) used progesterone for luteal support. Four studies were randomised controlled trials (RCTs), whereas the other four were historic cohort studies. In a meta-analysis using a random effects model, hCG administration for LPS did not increase the clinical pregnancy rate (CPR) (two studies, odds ratio (OR) 0.85, 95% CI 0.64–1.14). On the other hand, progesterone LPS was associated with a higher CPR (five studies, OR 1.48, 95% CI 1.14–1.94), and a higher live birth rate (LBR) (three studies, OR 1.67, 95% CI 1.19–2.36). The association between progesterone LPS and the LBR remained significant after excluding non-randomised studies.

 FET 於取卵後１週期懷孕率高於取卵後2-3週期

Immediate versus postponed frozen embryo transfer after IVF/ICSI: a systematic review and meta-analysis

Human Reproduction Update, Volume 27, Issue 4, July-August 2021, Pages 623–642, https://doi.org/10.1093/humupd/dmab002

BACKGROUND

In Europe, the number of frozen embryo transfer (FET) cycles is steadily increasing, now accounting for more than 190 000 cycles per year. It is standard clinical practice to postpone FET for at least one menstrual cycle following a failed fresh transfer or after a freeze-all cycle. The purpose of this practice is to minimise the possible residual negative effect of ovarian stimulation on the resumption of a normal ovulatory cycle and receptivity of the endometrium. Although elective deferral of FET may unnecessarily delay time to pregnancy, immediate FET may be inefficient in a clinical setting, following an increased risk of irregular ovulatory cycles and the presence of functional cysts, increasing the risk of cycle cancellation.

OBJECTIVE AND RATIONALE

This review explores the impact of timing of FET in the first cycle (immediate FET) versus the second or subsequent cycle (postponed FET) following a failed fresh transfer or a freeze-all cycle on live birth rate (LBR). Secondary endpoints were implantation, pregnancy and clinical pregnancy rates (CPR) as well as miscarriage rate (MR).

SEARCH METHODS

We searched PubMed (MEDLINE) and EMBASE databases for MeSH and Emtree terms, as well as text words related to timing of FET, up to March 2020, in English language. There were no limitations regarding year of publication or duration of follow-up. Inclusion criteria were subfertile women aged 18-46 years with any indication for treatment with IVF/ICSI. Studies on oocyte donation were excluded. All original studies were included, except for case reports, study protocols and abstracts only. Covidence, a Cochrane-tool, was used for sorting and screening of literature. Risk of bias was assessed using the Robins-I tool and the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework.

OUTCOMES

Out of 4124 search results, 15 studies were included in the review. Studies reporting adjusted odds ratios (aOR) for LBR, CPR and MR were included in meta-analyses. All studies (n = 15) were retrospective cohort studies involving a total of 6,304 immediate FET cycles and 13,851 postponed FET cycles including 8,019 matched controls. Twelve studies of very low to moderate quality reported no difference in LBR with immediate versus postponed FET. Two studies of moderate quality reported a statistically significant increase in LBR with immediate FET and one small study of very low quality reported better LBR with postponed FET. Trends in rates of secondary outcomes followed trends in LBR regarding timing of FET. The meta-analyses showed a significant advantage of immediate FET (n =2,076) compared to postponed FET (n =3,833), with a pooled aOR of 1.20 (95% CI 1.01–1.44) for LBR and a pooled aOR of 1.22 (95% CI 1.07–1.39) for CPR.