臨床婦人科産科76巻4号

2022年04月発行

増刊号 最新の不妊診療がわかる！―生殖補助医療を中心とした新たな治療体系 第3章　生殖補助医療の調節卵巣刺激 内因性LHサージ抑制法

プロゲステロンによる新しい内因性LHサージ抑制―PPOS法による調節卵巣刺激

著者： 山田愛¹ 塩谷雅英¹

所属機関： ¹英ウイメンズクリニック

ページ範囲：P.165 - P.170

▶progestin primed ovarian stimulation（PPOS）法は，プロゲスチンを内服しつつ刺激を行う，全凍結を前提とした新しい調節卵巣刺激法である．
▶PPOS法は，調節卵巣刺激中のLHサージ抑制効果を有し，従来のアゴニスト法やアンタゴニスト法と比較して遜色のない採卵成績および臨床妊娠率が得られる方法である．
▶プロゲスチン剤の選択と至適投与量，開始のタイミング，トリガーの選択に関する知見が積み重なり，幅広く臨床応用されるに至っている．

参考文献

1）Kuang Y, et al : Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril 104 : 62-70.e3, 2015

2）Richter TA, et al : Progesterone blocks the estradiol-stimulated luteinizing hormone surge by disrupting activation in response to a stimulatory estradiol signal in the ewe. Biol Reprod 67 : 119-125, 2002

3）Letterie GS, et al : Inhibition of gonadotropin surge by a brief mid-cycle regimen of ethinyl estradiol and norethindrone : possible role in in vitro fertilization. Gynecol Endocrinol 14 : 1-4, 2000

4）Cakmak H, et al : Effective method for emergency fertility preservation : random-start controlled ovarian stimulation. Fertil Steril 100 : 1673-1680, 2013

5）Ubaldi FM, et al : Follicular versus luteal phase ovarian stimulation during the same menstrual cycle（DuoStim） in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate : new insight in ovarian reserve exploitation. Fertil Steril 105 : 1488-1495.e1, 2016

6）Marshall JC, et al : Gonadotropin-releasing hormone pulses : regulators of gonadotropin synthesis and ovulatory cycles. Recent Prog Horm Res 47 : 155-187, 1991

7）Skinner DC, et al : The negative feedback actions of progesterone on gonadotropin-releasing hormone secretion are transduced by the classical progesterone receptor. Proc Natl Acad Sci U S A 95 : 10978-10983, 1998

8）Ohtaki T, et al : Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411 : 613-617, 2001

9）Kotani M, et al : The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276 : 34631-34636, 2001

10）中塚　愛，他 : Medroxyprogesterone acetate（MPA）を併用した新しい調節卵巣刺激法の有効性について．日受精着床会誌34 : 34-38, 2017

11）Wikström A, et al : The plasma concentration of medroxyprogesterone acetate and ovarian function during treatment with medroxyprogesterone acetate in 5 and 10mg doses. Acta Obst et Gynecal Scand 63 : 163-168, 1984

12）Dong J, et al : The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10mg of MPA per day in infertile women undergoing IVF : a randomized controlled trial. BJOG 124 : 1048-1055, 2017

13）Yildiz S, et al : Comparison of a novel flexible progestin primed ovarian stimulation protocol and the flexible gonadotropin-releasing hormone antagonist protocol for assisted reproductive technology. Fertil Steril 112 : 677-683, 2019

14）Turkgeldi E, et al : Effectiveness of the flexible progestin primed ovarian stimulation protocol compared to the flexible GnRH antagonist protocol in women with decreased ovarian reserve. Human Fertil（Camb） 16 : 1-7, 2020

）内服を用いた新しい調整卵巣刺激法．日受精着床会誌35 : 47-54, 2018

）の至適投与量の検討．日受精着床会誌37 : 177-182, 2020

17）Yu S, et al : New application of dydrogesterone as a part of a progestin-primed ovarian stimulation protocol for IVF : a randomized controlled trial including 516 first IVF/ICSI cycles.Hum Reprod 33 : 229-237, 2018

18）菊池　卓，他 : Chlormadinoe acetate（CMA）を使用したprogestin primed ovarian stimulation（PPOS）の有用性について．日受精着床会誌36 : 268-274, 2019

19）Takeshige Y, et al : Dose-dependent chlormadinone acetate can suppress premature LH surge in parallel with LH value reduction. Fertil Reprod 2 : 21-26, 2020

20）Lu X, et al : Dual trigger for final oocyte maturation improves the oocyte retrieval rate of suboptimal responders to gonadotropin-releasing hormone agonist. Fertil Steril 106 : 1356-1362, 2016

21）Kummer NE, et al : Predicting successful induction of oocyte maturation after gonadotropin-releasing hormone agonist（GnRHa）trigger. Hum Reprod 28 : 152-159, 2013

22）Practice Committee of the American Society for Reproductive Medicine : Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome : a guideline. Fertil Steril 106 : 1634-1647, 2016

23）Wang Y, et al : Controlled ovarian stimulation using medroxyprogesterone acetate and hmg in patients with polycystic ovary syndrome treated for IVF : a double-blind randomized crossover clinical trial. Medicine（Baltimore） 95 : e2939, 2016

24）Xiao ZN, et al : Flexible GnRH antagonist protocol versus progestin-primed ovarian stimulation（PPOS）protocol in patients with polycystic ovary syndrome : comparison of clinical outcomes and ovarian response. Curr Med Sci 39 : 431-436, 2019

25）Eftekhar M, et al : Progesterone-primed ovarian stimulation in polycystic ovarian syndrome : an RCT. Int J Reprod Biomed 17 : 671-676, 2019

26）Wang N, et al : Comparison of a progestin-primed ovarian stimulation protocol with a flexible GnRH antagonist protocol in patients with polycystic ovary syndrome who are participating in an IVF programme : study protocol for a randomised controlled trial. BMJ Open 10 : e038153, 2020