EMBRYOSCOPE – Time Lapse System

EMBRYOSCOPE 8 TIME-LAPSE SYSTEM
 -PURPOSE For embryo culture and evaluation- 
世界最先端受精卵培養画像解析装置、当院2020年より導入し、現在原則的全症例を対象に使用しています。

EBRYOSCOPEは受精卵を培養器内の密封された環境で連続的に胚を顕微鏡下に撮影するTime-pluse systemの装置です。標準的な培養方法と比べて、すべての年齢層の患者に対する流産率の低下、妊娠率と生産率の向上報告されている。こちらも・・・

EmbryoScopeの参考:
体外受精時における受精卵の発育-初期胚の評価と妊娠率の関係
体外受精時における受精卵の発育-胚盤胞の評価法と妊娠率の関係

エンブリオ・グルー EmbryoGlue

Embryo Glue® (エンブリオグルー)はヒアルロン酸入り胚移植用培養液です。 (グルー≒糊、接着剤)
「ヒアルロン酸(hyaluronic acid)は保水性が高く粘性を持つ特性がある。生体内に広く分布し、皮膚、軟骨、眼球では重要な役割を持つ。美容を目的とした注射はFDAによる医療承認がある。保湿成分として化粧品に添加され、健康食品でも膝の違和感や乾燥肌に対する機能性表示がある。」
ヒアルロン酸は卵胞液、卵管分泌液、子宮内腔にも自然に存在し、胚の着床を助けると考えられている。ヒアルロン酸は粘着性のあるムコ多糖類で胚盤胞の着床を促進する効果と受精卵の保護作用(ヒアルロン酸に包み込まれることで胚が外界からの様々なストレスを受けるのを防止する)を持つ生理的接着剤。

Embryo Glue® はVitrolife社製、FDA(米国食品医薬品局)に認可されており、受精卵に対して安全で優秀かつ高価な培養液であることです。この培養液の使用より着床率、臨床妊娠率が高くなる可能性があると多く報告されている。
当院では2014年1月より胚移植(新鮮胚移植、凍結‐融解胚移植)の多く症例に対してEmbryo Glue®を使用し、良い成績を得ている。

 
Meta-Analysis
 
2020 Sep 2;9:CD007421.
 doi: 10.1002/14651858.CD007421.pub4.

Hyaluronic acid in embryo transfer media for assisted reproductive technologies

Affiliations 

PMID: 32876946
DOI: 10.1002/14651858.CD007421.pub4

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アシステッド・ハッチング  AHA

HCG子宮内注入法

HCG500IU子宮内注入法EG (Embryo Glue)なし

EGなしHCG500IU子宮内注入法

HCG500IU子宮内注入法EG (Embryo Glue)あり

EGありHCG500IU子宮内注入法

参考資料

Investigating the Optimal Time for Intrauterine Human
Chorionic Gonadotropin Infusion in Order to Improve IVF
Outcome: A Systematic Review and Meta-Analysis

Abstract.

Background/Aim: Studies on the impact of intrauterine human Chorionic Gonadotropin (hCG) administration in order to improve the In Vitro Fertilization (IVF) outcome have yielded conflicting results. The aim of the present systematic review and meta-analysis is to investigate whether timing of intrauterine hCG administration prior to embryo transfer affects its efficiency.

Materials and Methods:
A systematic search of the literature on Pubmed/Medline, Embase and Cochrane databases was performed. Only Randomized Control Trials were included in this metaanalysis.
Results:

Live birth rates were not improved
following hCG administration (RR=1.13, 95%CI=0.88-1.46, p=0.34) in the pooled results. Combined live birth and ongoing pregnancy rates were borderline statistically significant following hCG administration (RR=1.27, 95%CI=1.00-1.62, p=0.05). Following subgroup analysis regarding live birth and ongoing pregnancy rates, only the 5-12 minutes prior to the embryo transfer group reported a statistically significant improvement. Conclusion: Intrauterine infusion of hCG within an IVF-Intracytoplasmic Sperm Injection (ICSI) cycle improves outcome only when administered 5-12 min prior to embryo transfer.

https://www.researchgate.net/publication/336898051_Investigating_the_Optimal_Time_for_Intrauterine_Human_Chorionic_Gonadotropin_Infusion_in_Order_to_Improve_IVF_Outcome_A_Systematic_Review_and_Meta-Analysis

Intrauterine injection of human chorionic gonadotropin
improves pregnancy outcome in patients with repeated
implantation failure in frozen-thawed embryo transfer

ABSTRACT Objective: To investigate whether intrauterine injection of human chorionic gonadotropin (hCG)
before the embryo transfer in a frozen-thawed transfer cycle can improve the pregnancy outcome in the patients with repeated implantation failure (RIF).
Methods: Prospective randomized-controlled trial was adopted. A total of 140 patients, who underwent thawed embryo transplantation and were in line with the diagnosis of RIF, were included. Other patients with some factors, such as uterine malformation, postoperative uterine
cavity sticking, tubal effusion, endocrine diseases and endometriosis, were excluded. The patients
were randomly divided into 2 groups through the computer random number table: an hCG
intrauterine perfusion group and a control group. There was no significant difference in the age,
the estradiol level, the number of transplanted embryos, the number of optimal embryos, and
the thickness of the endometrium before transplantation between the 2 group (all P>0.05). The hCG+G2 fluid and the G2 fluid were prepared on the day of embryo transfer, and 40 μL of which
was injected at an intrauterine site at 3 minutes before embryo transfer in the hCG intrauterine
perfusion group and the control group, respectively. The clinical pregnancy rate and implantation
rate in the 2 groups were compared.
Results: The implantation rate (28.99%(40/138) vs 17.99%(25/139) )and the clinical pregnancy rate (52.17%(36/69) vs 30.88%(21/68) ) in the hCG intrauterine perfusion group were higher than those in the control group (both P<0.05).
Conclusion: The intrauterine injection of hCG can improve the implantation rate and pregnancy
rate in cryopreserved embryo transfer in patients with RIF.     

Effect of intrauterine injection of human chorionic gonadotropin before
frozen–thawed embryo transfer on pregnancy outcomes in women with endometriosis

Abstract
Objective: To investigate the effect of human chorionic gonadotropin (hCG) intrauterine injection
before frozen–thawed embryo transfer (FET) in women with endometriosis.
Methods: This retrospective cohort study included 45 women with endometriosis who underwent
hCG intrauterine injection before FET; each woman was matched with three patients with
endometriosis who did not receive hCG intrauterine injection (controls).  0.04 mL of r-hCG intrauterine injection 1 day before FET.   Data on pregnancy and
prenatal outcomes were extracted from medical records and compared.
Results: Patients in the hCG intrauterine injection group had significantly higher rates of pregnancy
and clinical pregnancy (64.4% and 57.8%, respectively) than controls (47.4% and 39.3%,
respectively). Neonatal birth weight for both singletons and twins was significantly higher
in the hCG group (3486458 g and 2710437 g, respectively) than in the control group
(3195±401 g and 2419±370 g, respectively).
Conclusion: Pregnancy rate, clinical pregnancy rate, and birth weight were improved in women
with endometriosis who underwent intrauterine hCG injection compared with those who did not receive hCG before FET.

Effect of intrauterine injection of human chorionic gonadotropin before fresh embryo transfer on IVF and ICSI outcomes: a meta‑analysis

Abstract
Purpose This analysis was performed to evaluate the effects of intrauterine injection of human horionic gonadotropin (hCG) before fresh embryo transfer (ET) on the outcomes of in vitro ertilization and intracytoplasmic sperm injection.
Methods Randomized controlled trials (RCTs) were identified by searching electronic databases. The outcomes of live birth, clinical pregnancy, implantation, biochemical pregnancy, ongoing pregnancy, ectopic pregnancy, and miscarriage
between groups with and without hCG injections were analyzed. Summary measures were reported as risk ratios (RR) with 95% confidence intervals.
Results Six RCTs on fresh embryo transfer (ET) were included in the meta-analysis. A total of 2759 women undergoing fresh ET were enrolled (hCG group n = 1429; control group n = 1330). Intrauterine injection of hCG significantly increased
rates of biochemical pregnancy (RR 1.61) and ongoing pregnancy (RR 1.58) compared to controls. However, there were no significant differences in clinical pregnancy (RR 1.11), implantation (RR 1.17), miscarriage (RR 0.91), ectopic (RR 1.65) or live birth rates (RR 1.13) between the hCG group and control group.
Conclusion The current evidence for intrauterine injection of hCG before fresh ET does not support its use in an assisted reproduction cycle.

SEET法 と 二段階胚移植法  

SEET法(Stimulation of Endometrium Embryo Transfer:子宮内膜刺激胚移植)

SEET法の考え
自然妊娠において、受精した卵子(胚)は細胞分裂を繰り返しながら成長を続け、5-6日目に着床が可能な胚盤胞と進め、子宮腔内に到着します。胚は卵管の中で成長をしながら子宮に向けて伝達物質(signal)を送って子宮内膜を刺激し、数日後に子宮内腔に到着する胚の着床しやすい子宮内膜の状態を作り出す。

SEET法の手順
① 体外受精の受精卵を5日間培養し、育った胚盤胞は凍結保存する。
② その際に使用された培養液を、胚盤胞とは別の容器に封入し-20℃に凍結保存する。(この培養液の中に、受精卵が成長する過程に排出される伝達物質が含まれています。)
③ 移植周期に胚培養液を解凍して子宮内に注入する。
  例:HRC(ホルモン補充周期)において、黄体補充を行ってから5(6)日目に胚盤胞移植する予定の場合に2(3)日目に解凍した胚培養液約20μlを子宮内腔に注入する。その3日後に胚盤胞を移植する。

参考資料:

Fertil Steril. 2007 Nov;88(5):1339-43.
doi: 10.1016/j.fertnstert.2007.01.011. Epub 2007 Jun 7.
Stimulation of endometrium embryo transfer (SEET): injection of embryo culture supernatant into the uterine cavity before blastocyst transfer can improve implantation and pregnancy rates
Sakae Goto 1, Takashi Kadowaki, Hiromi Hashimoto, Shoji Kokeguchi, Masahide Shiotani

Cochrane Database Syst Rev. 2020 Aug 14;8(8):CD013063.
doi: 10.1002/14651858.CD013063.pub2.
Endometrial injection of embryo culture supernatant for subfertile women in assisted reproduction
Charalampos S Siristatidis 1, Eleni Sertedaki 2, Vasilios Karageorgiou 3, Dennis Vaidakis 4

臨床婦人科産科 74巻12号 (2020年12月)
SEET法・二段階胚移植法の現状と効果
後藤 栄 11後藤レディースクリニックpp.1226-1235発行日 2020年12月10日

二段階胚移植法

二段階胚移植法は、初期胚(受精後2~3日目)をまず1個移植し、更に2~3日後に胚盤胞(受精後5~6日目)を1個移植する方法です。
1段階目の初期胚移植が、胚の伝達物質(signal)を子宮に届け、内膜を着床しやすくなる状態を誘導し、次に2段階目の胚盤胞移植の着床率が高まることを期待する。
しかし、合計2個の胚を移植するこの方法は多胎妊娠になる可能性も高くなる、当院は原則的行われていない。