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「トリガー」の習作(5)

ではGnRHanalogでtriggerをかける際、使用するanalogで差はあるのか?

何語の論文だ?フランス語?
hCGに比べると黄体期が短いが、使うanalogで有意差はない。
なんでもいいわけだ。


Triptorelin 0.2 mg and leuprolide 1 mg subcutaneous injections for triggering final follicular maturation were compared in patients with a high risk for ovarian hyperstimulation syndrome (OHSS).

どっちも変わらない、と。

Thus, at present, although dosing and type of GnRHa vary in the literature, there is insufficient evidence to support preferential use of any GnRHa over another.

ということで、今のところどれが優れている、というのは別にない、ということで良さそう。

「トリガー」の習作(4)

hCGと同様にGnRHanalogが(hypo-hypo以外のtriggerに使えるわけです(もちろんLongやらShortでは使えませんが~この点がantagonist法の利点です)。
ではGnRHanalogのtriggerについて見ていきます。

GnRHas displace the GnRH antagonist from the GnRH receptor, leading to receptor activation and gonadotropin release from the pituitary gland.
ということで、GnRH antagonistはcompetitive antagonistということですね。
ただし、antagonistを打ってから時間がたっていないとanalogのtrigger効果が出ない、と聞いたことがあります。
何時間空けばいいんでしょうか?

で、GnRH analogも、GnRHそのものではないわけです。
10アミノ酸のペプチド(でしたっけ?)の1か所ないし数か所を変えて、半減期が長くなっているわけでした。
(これ、ドクター『I』の大学の産婦人科の卒試の問題でしたwww)

The endogenous LH surge lasts ~48 hours and consists of three distinct phases, whereas LH secretion following GnRHa is characterized by two phases, that is, a rapid ascending phase lasting 4 hours, and a longer descending phase.
なるほど。GnRH analogのtriggerも完全に内因性のLHサージを模写できているわけではないわけですね。

GnRHa activates pituitary GnRH receptors to release both endogenous LH and FSH, whereas hCG possesses only LH-like activity.
Whereas the mid-cycle FSH surge is not critical for oocyte maturation to occur, FSH is known to increase LH receptor expression in granulosa cells and additionally may directly play a role in the expansion of cumulus–oocyte complexes and oocyte maturation.
ということで、話題のFSHサージはいるのかいらないのか??ないよりはマシレベルなのか???

「トリガー」の習作(3)

Although hCG activates the LH receptor, it does not do so in an identical manner to LH.

Receptors bound by hCG were immobile, whereas those bound by LH were rotationally mobile, potentially accounting for differences in receptor activation.

Furthermore, intracellular signaling following activation of the LH receptor differs depending on the ligand bound. hCG possesses higher affinity for the LH receptor than LH, and it is fivefold more potent in stimulating human granulosa cell cAMP activity than equimolar concentrations of LH. However, extracellular signal-related kinase 1/2 and AKT (protein kinase B) activation is greater following LH than hCG.

同じLH receptorのリガンドだが、リガンドごとに実は作用が違うんじゃないか、ってことだね。
LHにはLHの役割があり、hCGにはhCGの役割がある。
半減期の長短も当たり前だけど理由があるわけだ。

では、hCGなら尿由来製剤とリコンビナントはどうか?

the superiority of rhCG over uhCG has yet to be demonstrated, and two recent Cochrane reviews have found no difference in the rates of oocyte maturation, pregnancy outcomes, or OHSS.

コクランは同点。はリコンビナント250μgの勝ち。
urinary hCG may contain additional factors, such as epidermal growth factor (EGF), that could negatively influence trophoblast function.
か。

尿由来hCGがtriggerとして最低5000IIU必要としたのがこれだ。
採卵率でみてるんだ。

んじゃ、GnRHaはどうなんだ?
(また明日以降に)

「トリガー」の習作(2)

引き続き自習のメモ。

Although estradiol is key in initiation of the mid-cycle LH surge, levels of progesterone during the follicular phase are also influential.Administration of progesterone can advance the timing of the LH surge; coadministration of progesterone with estradiol results in an LH surge of greater duration and amplitude than by estradiol alone.
なるほど、LHサージはE2だけではないんだ。Pもね。

gonadotropin surge-attenuating factor (GnSAF) is a molecule produced by ovarian follicles that reduces pituitary sensitivity to GnRH and may act to attenuate the amplitude of the LH surge.
Differences in GnSAF have been proposed to contribute to the differential sensitivity to GnRH antagonism observed between cycles with monofollicular and multifollicular growth, whereby hypersecretion of GnSAF in cycles with multifollicular development may reduce the degree of GnRH
gonadotropin surge-attenuating factorなるほど。「サージ起こすな」っていうホルモンが内因性に存在するわけだ。で、
A marked decline in GnSAF activity in the late follicular phase allows for the expression of the mid-cycle gonadotropin surge and ovulation in women.
E2だけ見てもの論じるのもなるほど残念なわけだwww
E2だけじゃ決まらない。
そんなに甘くはないわな。

「トリガー」の習作(1)

ちょっと自習のメモ。

hCG has sufficient homology to LH to be able to activate the LH receptor and was the primary and remains the most commonly used trigger of oocyte maturation.

GnRHa induces endogenous gonadotropin (LH and FSH) release from the pituitary gland and is a safer option, particularly in women at high risk of OHSS.

Unfortunately, owing to the induction of a shorter duration of LH exposure, the luteal phase is more dysfunctional following GnRHa than hCG, and thus in recent years, there has been an interest in combining the better safety profile of GnRHa with a small dose of hCG to improve pregnancy rates, in socalled “double” or“dual” trigger protocol.

Although not in common clinical use, recombinant LH (rLH) has also been trialed as a possible alternative to hCG for inducing oocyte maturation.

More recently, kisspeptin, a neuropeptide that stimulates endogenous GnRH release, has been used to safely mature oocytes during IVF treatment even in women at high risk of OHSS,

the short protocol allows for the use of GnRHa or kisspeptin to inducefinal oocyte maturation, whereas hCG or rLH can be used in either short or long protocols.
(注:このshortは「ショート法」ではなく「アンタゴニスト法」のこと。)
The short protocol therefore enables greaterflexibility for the hormone stimulus to induce oocyte maturation.
This may be of particular value if the risk of OHSS only becomes apparent during follicular development.

やっぱ基本はアンタゴニスト法だね。

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ドクターI

Author:ドクターI
武蔵境生息、(自称)不妊屋「ドクターI」、自己流生殖医療を語ります。

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