出處:第一名的不孕症期刊 Hum Reprod Update. 2013年1月搶鮮版

 

卵巢庫存測試和病人的特點在預測卵巢反應和繼續妊娠的影響：病人個別特徵的研究。

抽象
背景雖然卵巢儲備測試（ORTS），是經常使用之前，試管嬰兒治療結果的預測，其預測值增值尚不清楚。我們評估了卵巢庫存測試和病人的特點，在預測IVF的結果的附加價值。方法對患者的個人數據（IPD）發表的研究報告進行綜合分析。 FSH，抗苗勒管激素（AMH）或基礎卵泡計數（AFC）的婦女接受試管嬰兒的研究和作者聯繫。使用隨機攔截logistic回歸模型，我們估計增加的預測值卵巢儲備測試（ORTS）相對於病人的特點，是否能增加預測試管嬰兒懷孕後的結果。

 

結果，我們能夠收集到28個數據庫，包括5705名婦女接受試管嬰兒。預測反應不佳的女性年齡在（AUC）下面積為0.61。 AFC和AMH顯著地提高了模型的擬合（P值<0.001）。此外，幾乎類似的準確率達到使用AMH和AFC獨自的（AUC分別為0.78和0.76）。結合這兩個測試，但是，並沒有提高反應不佳的預測（AUC 0.80，P = 0.19）。在預測試管嬰兒（IVF）後繼續妊娠，年齡是最好的單一預測（AUC 0.57），卵巢儲備測試（ORTS）如低的AMH，少的基礎濾泡(AFC)及高的FSH並且沒有對預測試管嬰兒（IVF）後繼續妊娠有任何價值，年齡對預測試管嬰兒（IVF）後繼續妊娠是最好的單一預測。結論這IPD薈萃分析表明，AFC和AMH明確添加到年齡在預測對預測試管嬰兒（IVF）後繼續妊娠反應不佳。作為單個試驗，AFC和AMH都完全預測卵巢低反應。相反的ORTS，沒有添加任何信息的能力有限，只有女性年齡來預測IVF後繼續妊娠。

 

陳醫師的意見:

卵巢庫存測試（ORTS）如低的AMH，少的基礎濾泡(AFC)及高的FSH並且沒有對預測試管嬰兒（IVF）後繼續妊娠有任何價值，年齡對預測試管嬰兒（IVF）後繼續妊娠是最好的單一預測。卵巢庫存測試（ORTS）如低的AMH，少的基礎濾泡(AFC)及高的FSH只能預測排卵藥刺激的反應。40歲不管卵巢庫存測試（ORTS）是否良好，仍有50%的流產率(多因染色體異常的胚胎，高齡的卵及胚胎易突變)。年齡才是測試管嬰兒（IVF）後繼續妊娠到不流產而染色體正常而生下來的關鍵。

 

 

原文

Hum Reprod Update. 2013 Jan;19(1):26-36. Epub 2012 Nov 27.

Added value of ovarian reserve testing on patient characteristics in the prediction of ovarian response and ongoing pregnancy: an individual patient data approach.

Broer SL, van Disseldorp J, Broeze KA, Dolleman M, Opmeer BC, Bossuyt P, Eijkemans MJ, Mol BW, Broekmans FJ; on behalf of the IMPORT study group.

Collaborators (35)

Broer SL, van Disseldorp J, Broeze KA, Dolleman M, Opmeer BC, Anderson RA, Ashrafi M, Bancsi L, Caroppo LE, Copperman A, Ebner T, Eldar Geva M, Erdem M, Greenblatt EM, Jayaprakasan K, Fenning R, Klinkert ER, Kwee J, Lambalk CB, La Marca A, McIlveen M, Merce LT, Muttukrishna S,Nelson SM, Ng HY, Popovic-Todorovic B, Smeenk JM, Tomás C, Van der Linden PJ, van Rooij IA, Vladimirov IK, Bossuyt PB, Eijkemans MJ, Mol BW, Frank B.

Source

Department of Reproductive Medicine, University Medical Center Utrecht , Room F05.126, P.O. Box 85500 , Utrecht 3508 GA, The Netherlands .

Abstract

BACKGROUND Although ovarian reserve tests (ORTs) are frequently used prior to IVF treatment for outcome prediction, their added predictive value is unclear. We assessed the added value of ORTs to patient characteristics in the prediction of IVF outcome. METHODS An individual patient data (IPD) meta-analysis from published studies was performed. Studies on FSH, anti-Müllerian hormone (AMH) or antral follicle count (AFC) in women undergoing IVF were identified and authors were contacted. Using random intercept logistic regression models, we estimated the added predictive value of ORTs for poor response and ongoing pregnancy after IVF, relative to patient characteristics. RESULTS We were able to collect 28 study databases, comprising 5705 women undergoing IVF. The area under the receiver-operating characteristic curve (AUC) for female age in predicting poor response was 0.61. AFC and AMH each significantly improved the model fit (P-value <0.001). Moreover, almost a similar accuracy was reached using AMH or AFC alone (AUC 0.78 and 0.76, respectively). Combining the two tests, however, did not improve prediction (AUC 0.80, P = 0.19) of poor response. In predicting ongoing pregnancy after IVF, age was the best single predictor (AUC 0.57), and none of the ORTs added any value. CONCLUSIONS This IPD meta-analysis demonstrates that AFC and AMH clearly add to age in predicting poor response. As single tests, AFC and AMH both fully cover the prediction of poor ovarian response. In contrast, none of the ORTs add any information to the limited capacity of female age to predict ongoing pregnancy after IVF. The clinical usefulness of ORTs prior to IVF will be limited to the prediction of ovarian response.

 

出處:第二名的不孕症期刊

 

Hum Reprod. 2013年1月 (搶鮮版)

2013年1月，28（1）:6-9

試管嬰兒以冷凍胚胎取代新鮮週期植入：為此最好的的時代做好準備了嗎？

 

英國的研究

 

傳統上，大多數在試管嬰兒（IVF）治療週期新鮮胚胎植入中的保留多餘的胚胎冷凍備用。隨著時間的推移冷凍保存設施的改善，鼓勵更多地使用這項技術(胚胎冷凍)成功率週期接近與新鮮胚胎移植的成功率。來自觀察性研究的數據表明，胚胎冷凍在產科和圍產兒結局是優於新鮮胚胎植入。在促進胎兒孕產婦安全的利益，因此它的時間，以避免新鮮胚胎移植試管嬰兒，凍結所有可用的胚胎，並取代他們在隨後的週期？在這篇文章中，我們探討這個概念的生物合理性，評價的證據基礎，並考慮採取這樣的策略，在常規臨床實踐的影響。現有的隨機試驗的結果出現有利於冷凍胚胎移植的策略，但可以考慮在臨床實踐中的重大變化之前，需要更大規模的試驗。

 

陳醫師的意見: 在優質的試管嬰兒中心普遍感受到冷凍胚胎植入懷孕率優於新鮮胚胎植入。這來自玻璃化(超快速)冷凍胚胎優於傳統的慢速冷凍胚胎植入。最重要的是產科結果是好的，有些學者或生殖中心鼓勵冷凍胚胎植入取代新鮮胚胎植入。我個人的臨床經驗亦覺得玻璃化(超快速)冷凍胚胎的懷孕率確實優良。但全球的生殖界及病患的觀念為此最好的時代做好準備了嗎?

 

 

Hum Reprod. 2013 Jan;28(1):6-9. doi: 10.1093/humrep/des386. Epub 2012 Nov 11.

Elective frozen replacement cycles for all: ready for prime time?

Maheshwari A, Bhattacharya S.

Source

Reproductive Medicine, Division of Applied Health Sciences, University of Aberdeen , Aberdeen Maternity Hospital , Aberdeen AB25 2ZL , UK .

Abstract

Conventionally, most in vitro fertilization (IVF) embryos are transferred in fresh treatment cycles with freezing reserved for spare ones. Improvement in cryopreservation facilities over time has encouraged the greater use of this technology with the success rate of frozen replacement cycles approaching that associated with fresh embryo transfer. Data from observational studies suggest that obstetric and perinatal outcomes are better in pregnancies resulting from frozen replacement cycles. In the interests of promoting feto-maternal safety is it therefore time to avoid fresh embryo transfers in IVF, freeze all available embryos and replace them in subsequent cycles? In this article we explore the biological plausibility of this concept, appraise the evidence underpinning it and consider the implications of adopting such a strategy in routine clinical practice. The outcomes of existing randomized trials appear to favour a strategy of frozen embryo transfer, but larger trials are needed before a major change in clinical practice can be considered.

 

前言

 

很多不孕患者看網路且在診間問著精胺酸(arginine) ，希望能提供醫學的實證來看看權威醫學期刊眼中的L-arginine精胺酸。

 

諾貝爾生理學或醫學獎 1998年

 

諾貝爾大會在斯德哥爾摩卡羅林斯卡研究所，瑞典，先後榮獲諾貝爾生理學或醫學獎為1998年羅伯特F Furchgott，路易Ĵ伊格納羅和穆拉德Ferid他們發現有關“一氧化氮作為信號分子在心血管系統“。

 

精胺酸是人體一氧化氮的來源，一氧化氮（NO）促使血管舒張，促進血液循環，醫學臨床研究強烈支持。一氧化氮，是一種短暫的，內源性氣體信號分子作為一個在體內。 Signal transmission by a gas, produced by one cell, which penetrates membranes and regulates the function of other cells is an entirely new principle for signalling in the human organism.信號傳輸的一種氣體，產生的一個細胞，滲入細胞膜的功能和調節其他細胞是一種全新的原則，在人類機體的信號。

 

精胺酸(arginine)是一胺基酸，為一氧化氮的前驅物。一氧化氮能使血管擴張，並認為精胺酸可以改善腎臟血流量。精胺酸在人體內參與許多的生理作用：例如肝臟中氨的代謝，精子的形成，傷口的癒合與免疫系統的維持等，也是肌肉形成的成份。精胺酸同時被多項醫學臨床研究證實具有改善性功能障礙及有效提高精子數量及活動力的臨床作用，多項針對精子活動力低及數量不足的不孕症夫妻所做的臨床研究發現，每天服用3-5公克的精胺酸，持續半年的研究發現，參與研究的夫妻增加了懷孕的訊息。

 

 

早在1975年的權威文獻提到精胺酸刺激體外精蟲和活動力

Biol Reprod. 1975 Sep;13(2):154-7.

L-arginine stimulation of human sperm motility in vitro.

 

因此有人認為，L -精胺酸提高精子活力的體外表現，它可能具有臨床價值與人類精液時低於正常運動時適利用人工受精。

 

——————————————————

 

1999年被發表研究試管嬰兒卵巢刺激反應差者

 Hum Reprod. 1999 Jul;14(7):1690-7.

Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients.

 

得出的結論是口服L -精胺酸在卵巢低反應患者可提高卵巢反應，子宮內膜容受性和懷孕率。

 

——————————————————

 

2010被研究L –精氨酸對子宮內膜和子宮血流量增長，提高子宮內膜厚度薄的患者子宮內膜的刺激與增厚。

 

 

Fertil Steril. 2010 Apr;93(6):1851-8. Epub 2009 Feb 6.

Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium.

結論（補）：維生素 E，L -精胺酸，或威而剛治療可改善子宮末稍血流，可能是有益於患者子宮內膜薄的改善。

 

 

L -精胺酸的醫學研究持續進行中，原來不孕患者口耳相傳的健康食品服用的行為也在蔓延著。

左:透明帶(殼)

右:著床的囊胚

摘自不孕症第一名的期刊Hum Reprod Update.

2011 Apr 7. [Epub ahead of print]

 

 

人類胚胎輔助孵化：

 

 

系統性回顧和綜合分析的隨機對照試驗

摘要

 

輔助孵化(剝殼或溶殼)（AH）的操縱是透明帶變薄或溶出小洞，目的是方便胚

 

胎孵化著床。方法系統評價和綜合分析醫學文獻是用來評價的效果啊對輔助生

 

育的結果：臨床妊娠率，活產，多胎妊娠和流產。額外的分析，在這些分組：

 

(一）新鮮胚胎移植到未特定狀況或者非預後不佳的婦女;（二）新鮮胚胎轉移

 

到婦女與以往多次的著床失敗;（三）新鮮胚胎轉移到高齡的婦女;（四）冷凍

 

胚胎轉移到未選定或非預後不良的婦女。結論是輔助孵化(剝殼或溶殼)對以前

 

的多次失敗的婦女或冷凍解凍胚胎增加臨床懷孕率和多胎率。不過，AH

 

輔助孵化(剝殼或溶殼)對新鮮胚胎來自未特定狀況或非預後不佳的婦女或高

 

齡的不孕婦女是不能提高臨床懷孕率的。由於小樣本納入研究，沒有適當

 

的結論可以得出關於流產或活產。 

原文

 

Assisted hatching of human embryos: a systematic review and meta-analysis of randomized controlled trials.

Martins WP, Rocha IA, Ferriani RA, Nastri CO.

 

Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirão Preto da, Universidade de São Paulo (DGO FMRP-USP), Av. dos Bandeirantes, 3900, Monte Alegre, 8 andar, Ribeirão Preto, SP 14049-900, Brasil, CEP.

 

Abstract

BACKGROUND Assisted hatching (AH) is a manipulation of zona pellucida aiming to facilitate embryo implantation. METHODS Systematic review and meta-analysis of medical literature was used to evaluate the effect of AH on assisted reproduction outcomes: clinical pregnancy, live birth, multiple pregnancy and miscarriage. Additional analysis was performed in these subgroups: (i) fresh embryos transferred to unselected or non-poor prognosis women; (ii) fresh embryos transferred to women with previous repeated failure; (iii) fresh embryos transferred to women of advanced age; (iv) frozen-thawed embryos transferred to unselected or non-poor prognosis women. Analyses were based on risk ratio and 95% confidence intervals (RR, 95% CIs) using Mantel-Haenszel random effects model. RESULTS There were 28 studies (5507 participants) included. AH was related to a trend toward increased clinical pregnancy for all participants (RR = 1.11, 95% CI = 1.00-1.24), with a significant increase in subgroups 2 (RR = 1.73; 95% CI = 1.37-2.17) and 4 (RR = 1.36; 95% CI = 1.08-1.72, P< 0.01), but not for subgroups 1 and 3. For multiple pregnancy, a significant increase was observed for all participants (RR = 1.45; 95% CI = 1.11-1.90) and for subgroups 2 (RR = 2.53; 95% CI = 1.23-5.21) and 4 (RR = 3.40; 95% CI = 1.93-6.01). No significant heterogeneity was observed in subgroup analysis. CONCLUSIONS AH was related to increased clinical pregnancy and multiple pregnancy rates in women with previous repeated failure or frozen-thawed embryos. However, AH is unlikely to increase clinical pregnancy rates when performed in fresh embryos transferred to unselected or non-poor prognosis women or to women of advanced age. Due to the small sample evaluated by the pool of included studies, no proper conclusions could be drawn regarding miscarriage or live birth.

 

 

 

我們常看到臨床的試管療程用上Aspirin，我自己也開，

 

 

大型匯總式的研究顯示阿司匹靈對試管療程

 

 

並不會增加懷孕率。

 

 

出處:第一名的不孕症期刊

 

Hum Reprod Update. 2011 Mar 21.

 

[Epub ahead of print]

 

 

阿司匹靈是否有效的改善婦女接受試管嬰兒的懷孕

 

 

率？結果是從個別病人的數據匯總分析

 

 

來自荷蘭的研究

 

 

摘要

 

 

阿司匹靈被認為可能提高試管嬰兒的療效，但以往傳統的分

 

 

析的結果是矛盾的。因此，我們進行了個別病人的數據的臨床

 

 

隨機試驗（RCTs）綜合分析關於這個問題。

 

結論是阿司匹靈並不能改善試管嬰兒的懷孕率。

 

原文 

Is aspirin effective in women undergoing in vitro fertilization (IVF)? Results from an individual patient data meta-analysis (IPD MA).

 

Groeneveld E, Broeze KA, Lambers MJ, Haapsamo M, Dirckx K, Schoot BC, Salle B, Duvan CI, Schats R, Mol BW, Hompes PG; the IPD MARIA study group.

 

Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, VU University Medical Centre, Amsterdam, The Netherlands.

 

Abstract

 

BACKGROUND Aspirin is believed to improve the outcome of IVF, but previous conventional meta-analyses on the subject are conflicting. Therefore, we performed a meta-analysis with individual patient data (IPD MA) of randomized clinical trials (RCTs) on the subject. METHODS A systematic literature search was conducted to identify RCTs assessing the effectiveness of aspirin in IVF. Authors were asked to share their original data. In a one step meta-analytic approach, the treatment effect of aspirin was estimated with odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression, based on the intention to treat principle. RESULTS Ten studies fulfilled the inclusion criteria. Authors of six studies provided IPD, including 1119 patients (562 placebo and 557 aspirin). There were 160 clinical pregnancies in the aspirin (28.8%) and 179 (31.9%) in the placebo group [OR 0.86, 95% CI (0.69-1.1)]. There were 129 ongoing pregnancies in the aspirin (23.6%) and 147 in the placebo group (26.7%) [OR 0.85, 95% CI (0.65-1.1)]. Whereas the conventional meta-analysis limited to studies that could provide IPD showed an OR of 0.89 (95% CI 0.69-1.2), the conventional meta-analysis limited to the eight studies of which method of randomization could be confirmed showed an OR of 0.94 (95% CI 0.76-1.17) and the conventional meta-analysis including all 10 eligible RCTs identified with our search changed the OR to 1.07 (95% CI 0.81-1.41). This difference in direction of effect, derived from the studies not able to share IPD of which quality of randomization could not be confirmed. CONCLUSIONS Aspirin does not improve pregnancy rates after IVF.

 

僅管如此，我相信很多人依舊會抱著至少沒害處，試管嬰兒的療程會繼續使用。

翻自權威的生殖期刊HUMAN REPRODUCTION

 

2011.04.30

 

奧地利的研究

 

婦女AMH極低的活產機會

 

摘要

背景:

研究婦女極低的AMH（<0.1-0.4 ng/ml）在人工生殖的治療後活產的能力與這樣的能力是否與年齡有關。

 

方法:

2006年1月至2009年10月連續 128例AMH ≤0.4 ng/ml的患者接受IVF治療進行回顧性的研究懷孕率和活產的機會。

 

結果:

患者提出了在平均（±標準差）年齡為 40.8 ± 4.1歲，平均（±標準差）FSH為15.7 ± 11.1 mIU / ml，且平均（±標準差）AMH為 0.2 ± 0.1 ng/ml。一百二十名婦女進行了總共接受了254個IVF週期。共20個IVF週期有臨床懷孕（7.9％每週期的開始 [95％可信區間（CI）：4.9-11.9％]; 15.6％的累積 [區間：9.8-23.1％]）。20個婦女驗孕成功(clinical pregnancy)，有12名懷孕婦女（即11個單胞胎和一對雙胞胎）共產下13個活產嬰兒和8例懷孕婦女流產。8位生產是第一個IVF週期（每週期開始 6.3％）和4個生產在隨後的IVF週期（3.2％）。依女性的年齡計算，70名婦女≤42歲共有16個臨床妊娠懷孕，而其中10例（14.3％）活產，而58例>42歲有4個臨床懷孕，其中2例活產（3.4％），相較於小於42歲的族群顯著減少懷孕的機會（P = 0.013）和生產率（P = 0.036）。

 

結論:

極低的AMH，中等但合理的懷孕率和活產率仍然是可能的。極低的AMH並不能代表唯一的指標而暫緩生育治療。

 

原文

 

Hum Reprod. 2011 Apr 30.

 

Live birth chances in women with extremely low-serum anti-Mullerian hormone levels.

Weghofer A, Dietrich W, Barad DH, Gleicher N.

Source

Department of Obstetrics and Gynecology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

Abstract

BACKGROUND To determine whether women with extremely low-serum anti-Mullerian hormone (AMH) levels (<0.1-0.4 ng/ml) still demonstrate live birth potential with assisted reproduction and whether such potential is age dependent. METHODS Between January 2006 and October 2009, 128 consecutive infertility patients with AMH ≤0.4 ng/ml were retrospectively evaluated for pregnancy chances and live birth rates after IVF. RESULTS Patients presented at a mean (±SD) age of 40.8 ± 4.1 years, with mean (±SD) baseline FSH of 15.7 ± 11.1 mIU/ml and mean (±SD) AMH of 0.2 ± 0.1 ng/ml. One hundred and twenty-eight women underwent a total of 254 IVF cycles. Twenty clinical pregnancies were recorded (7.9% per cycle start [95% confidence interval (CI): 4.9-11.9%]; 15.6% cumulative [CI: 9.8-23.1%]). These pregnancies resulted in 13 live births in 12 women (i.e. 11 singletons and a pair of twins) and 8 patients miscarried. Eight deliveries occurred after the first cycle (6.3% per cycle start) and four after subsequent IVF cycles (3.2%). When evaluated according to female age, 70 women ≤42 years presented with 16 clinical pregnancies that resulted in 10 deliveries (14.3%), while 58 patients >42 years presented with four clinical pregnancies that resulted in 2 deliveries (3.4%), representing a reduced pregnancy chance (P = 0.013) and delivery rate (P = 0.036) versus age ≤42 years. CONCLUSIONS With extremely low-serum AMH levels, moderate, but reasonable pregnancy and live birth rates are still possible. Extremely low AMH levels do not seem to represent an appropriate marker for withholding fertility treatment.