COH全程使用排卵藥D2~打破卵針可下降排卵針使用量

全程使用排卵藥clomid (D2~打破卵針)可下降排卵針使用量
卵子品質數量與受孕率並無減少
為避免clomid對子宮內膜之不良影響, 全數胚胎冷凍下週期再植入

J Hum Reprod Sci. 2015 Jul-Sep;8(3):142-5. doi: 10.4103/0974-1208.165151.

Clomiphene based ovarian stimulation in a commercial donor program.

Gupta S1, Satwik R1, Majumdar A1, Mittal S1, Tiwari N1.

Author information

Abstract

OBJECTIVE:

This study was conducted to compare an extended clomiphene-based ovarian stimulation regimen with the conventional antagonist protocol in donor-recipient cycles.

MATERIALS AND METHODS:

A total of 170 (N) donors were stimulated between January 2013 and December 2013. Conventional antagonist protocol (group I) was employed in (n1 = 31) cycles, and clomiphene was used in (n2 = 139) donor cycles (group II). 50 mg clomiphene was given simultaneously with gonadotropins from day 2 of the cycle until the day of trigger. The analysis was performed retrospectively for oocytes retrieved, fertilization rates, cycle cancelation, blastocyst formation, and pregnancy rates. The dosages, cost, and terminal E2 (estradiol) were also compared between the two groups.

RESULTS:

The donor age groups were comparable in both the groups. There were no unsuccessful egg retrievals with clomiphene. The pregnancy rate (positive beta human chorionic gonadotropin) was significantly higher in the clomiphene group (odds ratio: 2.453; P = 0.02). Similarly, fertilization rate was significantly higher in the clomiphene group (59.5/50.5, P = 0.04). Eggs retrieved were similar in both groups, but the terminal E2 was significantly higher in the clomiphene group (P = 0.001). Average gonadotropin used was also significantly lower in clomiphene group (P < 0.001).

CONCLUSION:

Clomiphene can effectively prevent luteinizing hormone surge and limit the dose of gonadotropins thus bringing down the costs and its negative impact on the endometrium and oocyte quality.

使用elonva誘導排卵始於第4天效果明顯低於始於第2天

使用elonva誘導排卵始於第2天效果類似始於第4天
卵子數量無明顯差異 (12.8 vs 14.7)

始於第2天使用排卵針劑量明顯高於始於第2天(324 vs 173 iu)

Elonva 150ug使用於高齡反應差病患,效果類似puregon每天450iu

Elonva 150ug 單一劑量, 使用於高齡反應差病患, 效果類似puregon 450iu/d x 7d

高齡病患卵針劑劑量450 vs 600 iu 懷孕率無明顯差異

針對高齡反應差poor responder之病患
高劑量誘導排卵針劑劑量450 iu vs 600 iu
懷孕率(16 vs18)&取卵數(4 vs 4)無明顯差異

Fertil Steril. 2015 Sep 7. pii: S0015-0282(15)01851-8. doi: 10.1016/j.fertnstert.2015.08.014. [Epub ahead of print]

450 IU versus 600 IU gonadotropin for controlled ovarian stimulation in poor responders: a randomized controlled trial.

Lefebvre J1, Antaki R2, Kadoch JI2, Dean NL3, Sylvestre C4, Bissonnette F2, Benoit J4, Ménard S2, Lapensée L2.

Author information

Abstract

OBJECTIVE:

To compare the outcomes of controlled ovarian stimulation/in vitro fertilization cycles using 450 IU and 600 IU gonadotropin per day in women at risk of poor ovarian response.

DESIGN:

Prospective randomized controlled nonblinded study.

SETTING:

University-affiliated private IVF center.

PATIENT(S):

Women considered to be at risk of poor ovarian response: aged <41 years with basal FSH >10 IU/L, antimüllerian hormone <1 ng/mL, antral follicle count ≤8, or a previous IVF cycle with ≥300 IU/d gonadotropin that resulted in a cancellation, <8 follicles, or <5 oocytes.

INTERVENTION(S):

A total of 356 patients underwent a microdose GnRH agonist flare-up IVF/intracytoplasmic sperm injection protocol with a fixed daily dose of either 450 IU FSH (n = 176) or 600 IU FSH (n = 180) equally divided between Menopur and Bravelle.

MAIN OUTCOME MEASURE(S):

Number of mature oocytes retrieved.

RESULT(S):

The two groups were similar in terms of age, ovarian reserve, cause of infertility, duration of stimulation, and cycle cancellation rate. There were no significant differences in the number of metaphase II oocytes retrieved (4 [range 0-6] vs. 4 [range 2-7]), fertilization rate (62.4% vs. 57.0%), biochemical pregnancy rate (20.5% vs. 22.9%), clinical pregnancy rate (16.4% vs. 18.3%), and implantation rate (29.8% vs. 30.4%) between the 450 IU and 600 IU groups, respectively.

CONCLUSION(S):

Gonadotropin of 600 IU/d does not improve outcome of IVF cycles compared with 450 IU/d in women at risk of poor ovarian response.

HCG使用於誘導排卵可能會干擾胚胎著床率

HCG (750iu/3d)使用於誘導排卵COH 期間，可能會干擾胚胎著床率

http://humrep.oxfordjournals.org/external-ref?access_num=19165663&link_type=MED

過早或過長使用hCG可能導致子宮內膜老化

COH過程中，過早或過長使用hCG，可能導致子宮內膜老化進而干擾胚胎著床

hCG會刺激卵巢黃體與子宮內膜之LH接受體,

http://humrep.oxfordjournals.org/content/28/6/1610.full

施打hCG於COH末期，造成FSH & LH 下降

施打hCG於COH末期，造成FSH & LH 下降
施打hCG於COH末期, 懷孕率高於傳統COH(37  vs  29%)
施打hCG於COH末期, rFHS 劑量低於傳統COH(1273 vs 1617iu)

http://humrep.oxfordjournals.org/content/24/11/2910.full

COH過程需考量2波FSH window

長療程可能優於短療程
pill+fixed GnRHantagonist可能優於flexible  GnRHantagonist

 we believe that stable and early suppression of endogenous gonadotrophins may be advantageous to achieve follicular synchronization and the highest clinical pregnancy rates. This may be achieved by either a long GnRH agonist protocol or a ‘long’ GnRH antagonist protocol (i.e. OC pretreated fixed GnRH antagonist protocol). In this respect, short or flexible regimens seem to be far from optimal. 

誘導排卵COH過程需考量2波FSH window




http://humrep.oxfordjournals.org/content/22/11/2805.full

clomid使用於誘導排卵會造成子宮內膜延後黃體化1-2天

FSH使用於誘導排卵會造成子宮內膜提早黃體化1-2天

clomid使用於誘導排卵會造成子宮內膜延後黃體化1-2天&子宮內膜變差
reduction of pinopod formation in the mid-luteal phase (Creus et al., 2003). 
The glandular density is reduced 

http://humupd.oxfordjournals.org/content/12/5/617.full

COH時間越長,可能造成子宮內膜老化, 進而降低懷孕率

COH時間越長, 延長濾泡期, 植入時間往後延後之結果，可能造成子宮內膜受E2刺激時間延長,造成子宮內膜老化,  進而降低懷孕率

http://humrep.oxfordjournals.org/content/21/4/1012.full

延後2天取卵可取較多卵子

傳統取卵時機為達3顆卵子>1.7cm
若不考慮內膜老化因素(轉為冷凍胚胎保存), 延後2天取卵可取較多卵子,

http://humrep.oxfordjournals.org/content/20/9/2453.full

http://www.ncbi.nlm.nih.gov/pubmed/15236997?dopt=Abstract

用hCG 200 iu 取代FSH於晚期誘導排卵

卵>1.2cm可以使用hCG 200 iu/d 取代FSH於誘導排卵

http://molehr.oxfordjournals.org/content/17/1/33.full

hCG100-150iu誘導排卵可達不錯IVF懷孕率

IVF誘導排卵COH配合FSH+hCG100-150iu可達不錯懷孕率

http://humrep.oxfordjournals.org/content/27/10/3074.full

COH後,子宮內膜PR 表現上升, ER表現下降

COH後,子宮內膜PR 表現上升, ER表現下降

優質胚胎可能可克服較差(P4上升)之內膜環境

Day 2-3胚胎著床率IR約10-15%

http://humrep.oxfordjournals.org/content/20/6/1541.full

IVF藥物會影響子宮內膜之基因表現

誘導排卵COH藥物會影響子宮內膜之基因表現，進而干擾胚胎著床

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871799/?report=reader

卵泡成長週期中有2-3個生長波

自然狀況下人類排卵時卵泡大小約2cm,
卵泡成長週期中，約有2-3個生長波

http://www.cbra.org.br/pages/publicacoes/animalreproduction/issues/download/v6n1/pag%2020-29.pdf

卵泡生長波由多次複合生長波組成

卵泡生長波由多次複合生長波組成，包括主波, 次波, 3rd波
主波形成之優勢卵泡較次波, 3rd波形成之優勢卵泡為大

http://www.sciencedirect.com/science/article/pii/S0737080607800128

COH反應以COH 4天後卵巢反應為準

AMH, AFC是COH前預測卵巢反應之最有效工具

但COH劑量調整仍應以COH 4天後卵巢反應為準

http://humrep.oxfordjournals.org/content/25/1/221.full

濾泡每日生長速度1-2mm

濾泡生長速度約1-4mm/d (平均1.33mm/d)

濾泡中期(day9)以後, 濾泡>0.9cm才有可能成熟

http://humupd.oxfordjournals.org/content/18/1/73.full#ref-22

GnRHantagonist療程不需事前使用pill

GnRHantagonist療程不需事前使用pill

使用pill 並不明顯提高懷孕率
反而提高COH劑量

http://www.ncbi.nlm.nih.gov/pubmed/18054003?dopt=Abstract