反覆流產之病患需篩檢是否輕微甲狀腺低下

反覆流產之病患需篩檢是否輕微甲狀腺低下([TSH] >2.5 mIU/L with a normal free thyroxine or free thyroxine index)

高達19%是因為輕微甲狀腺低下引發反覆流產

http://www.sciencedirect.com/science/article/pii/S0015028213027611

90%卵子在授精後6小時排出第二極體

90%卵子在授精後6小時排出第二極體
80%胚胎在授精後8小時可觀察到原核

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241845/

冷凍時間長短對懷孕率及畸形率無明顯影響

比較囊胚期胚胎玻璃化冷凍1年及超過6年以上，
冷凍時間長短對於胚胎懷孕著床率及胎兒畸形率無明顯影響

http://humrep.oxfordjournals.org/content/28/11/2950.abstract

8細胞解凍胚胎能容許2胚葉細胞耗損，6-7細胞解凍胚胎僅能容許1胚葉細胞耗損

冷凍胚胎解凍後關鍵為是否有繼續分裂，
培養12小時(overnight)，若有繼續分裂，縱使解凍過程部分胚葉細胞耗損仍無損其未來著床率
8-cell胚胎能容許2胚葉細胞耗損
6-7cell胚胎僅能容許1胚葉細胞耗損
玻璃化冷凍優於慢速冷凍已成共識

http://humrep.oxfordjournals.org/content/28/11/2943.abstract

縮短IVF授孕時間可能可提高臨床懷孕率

縮短精蟲卵子IVF授孕時間，可能可提高臨床懷孕率，
但必須是非男性不孕症，精蟲活動力與數量在正常標準以上

http://www.ncbi.nlm.nih.gov/pubmed/?term=ime+of+insemination+culture+and+outcomes+of+in+vitro+fertilization

不明原因不孕可考慮ICSI避免卵子全無受精

不明原因不孕症之病患必要時須考慮精蟲顯微注射授精ICSI方式以避免卵子全無受精

http://www.sciencedirect.com/science/article/pii/S0015028213005529

35歲以上病患使用LH補充誘導排卵無明顯提高懷孕率

35歲以上病患使用LH補充誘導排卵並無明顯提高懷孕率，
FSH+LH vs. FSH  活產率為 20 vs 22%

http://www.ncbi.nlm.nih.gov/pubmed/23838159

GnRHantagonist不需提早在誘導排卵早期施打

提早施打GnRHantagonist (月經第2天)比常規施打GnRHantagonist (月經第7天)
臨床結果並無統計差異

http://www.ncbi.nlm.nih.gov/pubmed/24129613

子宮移植並冷凍胚胎植入成功懷孕

先天無子宮病患可成功子宮移植，並經由試管冷凍胚胎植入成功懷孕

http://www.ncbi.nlm.nih.gov/pubmed/23830110

泡期中後期後使用低劑量hCG效果類似傳統排卵針

於濾泡期中後期以後使用低劑量hCG (200iu/d)，效果類似傳統排卵針，
可產生不錯誘導排卵COH效果及IVF-ICSI懷孕率，

http://www.ncbi.nlm.nih.gov/pubmed/16084880?dopt=Abstract

玻璃化冷凍懷孕率達36%

胚胎玻璃化冷凍優於慢速冷凍
懷孕率達36%，類似新鮮胚胎懷孕率

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463664/

Table 3

Assisted reproduction outcomes of fresh cycles, slow freezing and vitrification

Parameters	Fresh cycle	Slow freezing	Vitrification	P-value (Fresh vs. Slow)	P-value (Fresh vs. Vitrification)	P-value (Slow vs. Vitrification)
General clinical data
Embryos Transferred	2.2±0.9	2.9±0.90	2.6±0.7	0.07	0.23	0.45
Implantation rate (%)	298/1448(20.6)	48/334(14.4)	142/719(19.8)	0.010α’	0.651	0.035
Clinical pregnancy rate (%)	239/657(36.4)	39/151(25.8)	109/300(36.3)	0.014α’	0.989	0.025
Multiple pregnancy rate(%)	58/657(8.8)	9/151(6.0	29/300(9.7)	0.249	0.675	0.181
Live birth (LB) rate (%)	225/657(34.3)	35/151(23.2)	106/300(35.3)	0.009α’	0.743	0.009α’
Loss of pregnancy
Early abortion rate(%)	23/239(9.6)	3/39(7.7)	18/109(16.5)	0.701	0.064	0.175
Late abortion rate(%)	15/239(6.3)	3/39(7.7)	2/109(1.8)	0.739	0.075	0.082
Induced abortion rate(%)	2/239(0.8)	1/39(2.6)	0	0.895	1.000	0.264
Ectopic pregnancy rate(%)	9/239(3.8)	0	4/109(3.7)	0.619	1.000	0.573
Mode of delivery
Spontaneous vaginal delivery rate(%)	34/190(17.9)	5/32(15.6)	6/85(7.1)	0.755	0.019	0.157

GnRHa於誘導破卵懷孕率較傳統hCG為低

使用腦下垂體拮抗劑GnRHa於誘導破卵懷孕率較傳統hCG為低(15 vs 30%)

http://www.ncbi.nlm.nih.gov/pubmed/21249699

小於3cm之子宮內膜異位瘤對IVF誘導排卵影響不顯注

小於3cm之子宮內膜異位瘤對於卵巢功能影響較不明顯，
對施行IVF誘導排卵COH之卵泡生成影響較不顯注

http://humrep.oxfordjournals.org/content/25/1/288.full

月經第一天施打hCG可提高IVF胚胎著床率

誘導排卵COH前 (月經第一天)施打hCG 5000iu可下降誘導排卵藥物劑量，提高胚胎之懷孕率與著床率

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729860/

IVF療程前使用黃體素比避孕藥可達更佳懷孕率

試管嬰兒療程前使用黃體素可能比使用避孕藥可達更佳懷孕率

試管嬰兒療程前使用避孕藥可能對卵巢功能及懷孕率有不良影響

http://www.ncbi.nlm.nih.gov/pubmed/20091585

長效與短效腦下垂體抑制劑IVF懷孕率無統計差異

長效腦下垂體抑制劑與短效腦下垂體抑制劑用於試管嬰兒，
懷孕率無統計差異 (25-35%  vs. 30%)
長效腦下垂體抑制劑需要較高劑量之排卵針

http://www.ncbi.nlm.nih.gov/pubmed/23440788

Cochrane Database Syst Rev. 2013 Jan 31;1:CD002808. doi: 10.1002/14651858.CD002808.pub3.

Depot versus daily administration of gonadotrophin-releasing hormone agonist protocols for pituitary down regulation in assisted reproduction cycles.

Albuquerque LE, Tso LO, Saconato H, Albuquerque MC, Macedo CR.

Source

Human Reproduction Center, Fertivitro Centro de Reprodução Humana, São Paulo, Brazil. leta@osite.com.br.

Abstract

BACKGROUND:

Gonadotrophin-releasing hormone agonist (GnRHa) is commonly used to switch off (down regulate) the pituitary gland and thus suppress ovarian activity in women undergoing in vitro fertilisation (IVF). Other fertility drugs (gonadotrophins) are then used to stimulate ovulation in a controlled manner. Among the various types of pituitary down regulation protocols in use, the long protocol achieves the best clinical pregnancy rate. The long protocol requires GnRHa administration until suppression of ovarian activity occurs, within approximately 14 days. GnRHa can be used either as daily low-dose injections or through a single injection containing higher doses of the drug (depot). It is unclear which of these two forms of administration is best, and whether single depot administration may require higher doses of gonadotrophins.

OBJECTIVES:

To compare the effectiveness and safety of a single depot dose of GHRHa versus daily GnRHa doses in women undergoing IVF.

SEARCH METHODS:

We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched July 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE (1966 to July 2012), EMBASE (1980 to July 2012) and LILACS (1982 to July 2012). We also screened the reference lists of articles.

SELECTION CRITERIA:

We included RCTs comparing depot and daily administration of GnRHa for long protocols in IVF treatment cycles in couples with any cause of infertility, using various methods of ovarian stimulation. The primary review outcomes were live birth or ongoing pregnancy, clinical pregnancy and ovarian hyperstimulation syndrome (OHSS). Other outcomes included number of oocytes retrieved, miscarriage, multiple pregnancy, number of gonadotrophin (FSH) units used for ovarian stimulation, duration of gonadotrophin treatment, cost and patient convenience.

DATA COLLECTION AND ANALYSIS:

Two review authors independently selected studies, extracted data and assessed study quality. For dichotomous outcomes, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) per woman randomised. Where appropriate, we pooled studies.

MAIN RESULTS:

Sixteen studies were eligible for inclusion (n = 1811 participants), 12 (n = 1366 participants) of which were suitable for meta-analysis. No significant heterogeneity was detected.There were no significant differences between depot GnRHa and daily GnRHa in live birth/ongoing pregnancy rates (OR 0.95, 95% CI 0.70 to 1.31, seven studies, 873 women), but substantial differences could not be ruled out. Thus for a woman with a 24% chance of achieving a live birth or ongoing pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 18% and 29%.There was no significant difference between the groups in clinical pregnancy rate (OR 0.96, 95% CI 0.75 to 1.23, 11 studies, 1259 women). For a woman with a 30% chance of achieving clinical pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 25% and 35%.There was no significant difference between the groups in the rate of severe OHSS (OR 0.84, 95% CI 0.29 to 2.42, five studies, 570 women), but substantial differences could not be ruled out. For a woman with a 3% chance of severe OHSS using daily GnRHa injections, the corresponding risk using GnRHa depot would be between 1% and 6%.Compared to women using daily GnRHa, those on depot administration required significantly more gonadotrophin units for ovarian stimulation (standardised mean difference (SMD) 0.26, 95% CI 0.08 to 0.43, 11 studies, 1143 women) and a significantly longer duration of gonadotrophin use (mean difference (MD) 0.65, 95% CI 0.46 to 0.84, 10 studies, 1033 women).Study quality was unclear due to poor reporting. Only four studies reported live births as an outcome and only five described adequate methods for concealment of allocation.

AUTHORS' CONCLUSIONS:

We found no evidence of a significant difference between depot and daily GnRHa use for pituitary down regulation in IVF cycles using the long protocol, but substantial differences could not be ruled out. Since depot GnRHa requires more gonadotrophins and a longer duration of use, it may increase the overall costs of IVF treatment.

AMH可做為化療前後卵巢功能恢復狀況之指標

AMH可在任何年紀(0.3–15 yr)女性偵測的到
經過化療治療後AMH & inhibin B均會下降
停止化療治療後AMH逐漸回復

AMH可做為化療前後卵巢功能恢復狀況之指標

http://jcem.endojournals.org/content/97/6/2059.full

IVM卵子以ICSI或IVF授精並無明顯差異

體外不成熟卵子經培養IVM後，再以ICSI或IVF授精後，胚胎受孕率或著床率並無明顯差異

http://www.ncbi.nlm.nih.gov/pubmed/23063820

Reprod Biomed Online. 2012 Dec;25(6):603-7. doi: 10.1016/j.rbmo.2012.08.001. Epub 2012 Aug 31.

IVF versus ICSI for the fertilization of in-vitro matured human oocytes.

Walls M, Junk S, Ryan JP, Hart R.

Source

Fertility Specialists WA, 25 Queenslea Drive, Claremont, Perth, Western Australia 6010, Australia. melanie@fertilitywa.com.au

Abstract

Traditional dogma suggests that intracytoplasmic sperm injection (ICSI) should be performed to ensure successful oocyte fertilization in an in-vitro maturation (IVM) cycle. This study postulated that there would be no difference in the fertilization rate when ICSI was compared with IVF. This hypothesis was tested in a randomized trial of IVF versus ICSI in IVM. A total of 150 immature oocytes were collected in eight cycles of IVM for patients diagnosed with polycystic ovarian syndrome (PCOS). Patients were primed with minimal FSH before transvaginal oocyte aspiration. Sibling oocytes were inseminated by 50% IVF and 50% ICSI. There was no significant difference in fertilization, useable or total blastocyst development between the two insemination technique groups. Clinical pregnancy results for combined fresh and cryopreserved transfers were identical between the two insemination techniques with a total of two fresh and five cryopreserved IVF-inseminated embryos resulting in three clinical pregnancies (42.9%) and five fresh and two cryopreserved ICSI-derived embryos resulting in three clinical pregnancies (42.9%). This research has shown IVF to be a legitimate fertilization technique for IVM oocytes in PCOS patients and provides a greater awareness of the use of a fertilization method previously not utilized with IVM. In-vitro maturation (IVM) is an alternative treatment method to traditional IVF. Due to the minimal use of stimulating hormones in this treatment, IVM has a lower risk of ovarian hyperstimulation syndrome, it can be used for fertility preservation in cancer patients and it is more cost conservative. Early research into the effects of IVM showed a hardening effect on the membrane surrounding the egg (the zona pellucida). It was initially believed that, to overcome this hardening in order to allow the egg to be fertilized, spermatozoa would need to be injected into the egg using intracytoplasmic sperm injection. Due to recent advances in hormonal stimulation protocols (FSH priming) and culture conditions, we postulated that, for patients suffering from polycystic ovarian syndrome (PCOS), fertilization, embryo development and clinical pregnancy would not be superior in the injected oocytes compared with those inseminated by IVF. We found that by using the two insemination techniques on sibling oocytes from eight PCOS patients, there was no significant difference in fertilization, useable or total blastocyst development (day 5 or 6 embryos) and that clinical pregnancy results were identical. This research provides a greater awareness of a fertilization technique which is not normally utilized for IVM treatment, providing a less invasive, more cost-effective approach for the patient.

活動精蟲達200萬/ml可達35%懷孕率

精蟲活動力會影響懷孕率
活動精蟲達200萬/ml可達35%懷孕率


http://molehr.oxfordjournals.org/content/17/8/453.full

Figure 1

Data adapted and interpreted from Hargreave and Elton (1983) who studied in vivo conception in 867 subfertile couples. Note the effective plateau in conception rates with higher concentrations of motile cells and reduced per cent conception below ∼2 million motile cells/ml (blue bar). Importantly, small changes in the concentration of motile cells, e.g. from 0.5 to 1 million/ml, can have a noticeable effect on the chances of conception. This is the zone where small changes in the proportion of motile cells, for example, with in vitro drug stimulation can have a noticeable effect on fertility. These data are consistent with many other studies in the literature.

囊胚植入前基因篩檢可明顯提高胚胎著床率

囊胚期胚胎植入前施行基因篩檢PGD[(qPCR)-based comprehensive chromosome screening (CCS)]，可明顯提高胚胎著床率(68>85%)‧

http://www.ncbi.nlm.nih.gov/pubmed/23731996

Day3 胚胎切片明顯會下降胚胎著床率

PGD之胚胎切片時機對胚胎有不同影響
Day3 胚胎切片明顯會下降胚胎著床率(30 vs 50%)
Day5 胚胎切片不明顯下降胚胎著床率(51% vs. 54%)

http://www.ncbi.nlm.nih.gov/pubmed/23773313

皮下黃體素注射與Crinone臨床效果無差異

皮下黃體素注射Prolutex與陰道凝膠黃體素Crinone對於IVF-ET臨床效果無差異

http://www.ncbi.nlm.nih.gov/pubmed/24140033

70%胚胎在著床前後或懷孕早期萎縮流產

高達70%胚胎在著床前後或懷孕早期萎縮流產
胚胎受孕形成後約有30%在著床前萎縮，30%在著床後萎縮，10%在懷孕後流產，最後約30%順利活產

http://molehr.oxfordjournals.org/content/16/12/886.full

誘導排卵有17%提早黃體化

人工授孕誘導排卵過程有17%病患有提早黃體化現象 (LH≥10 IU/l, progesterone>1 ng/ml)

http://humrep.oxfordjournals.org/content/21/3/632.full

受孕窗口

fertile window受孕窗口定義為:
子宮頸黏液可由精蟲穿越到排卵日，受孕窗口時間1-5天，平均3天

http://humrep.oxfordjournals.org/content/22/6/1652.full

inhibin越低代表卵巢反應較差

inhibin越低代表卵巢對於COH誘導排卵之反應可能較差

優勢卵泡之篩選發生於月經來前之黃體期末期

http://jcem.endojournals.org/content/87/12/5746.full

精蟲濃度低於4000萬仍可能下降懷孕率

正常精蟲濃度不應低於2000萬/ml
但精蟲濃度低於4000萬/ml仍可能會下降懷孕率

http://humupd.oxfordjournals.org/content/14/6/593.full

抽菸引發精蟲mRNA & 蛋白質表現異常

抽菸引發精蟲mRNA & 蛋白質表現異常 (histone-to-protamine ratios, protamine mRNA expression)

http://www.ncbi.nlm.nih.gov/pubmed/24112532

高反應試管嬰兒病人P4濃度大於1.5並不明顯下降懷孕率

一般試管嬰兒病人施打hCG當天的P4濃度>1.5 ng/mL，懷孕率明顯下降，

取卵超過18顆的高反應試管嬰兒病人，施打hCG當天的P4濃度>1.5並不明顯影響懷孕率

http://www.ncbi.nlm.nih.gov/pubmed/24083873

胚胎品質影響冷凍解凍之存活率

胚胎之品質亦影響冷凍解凍之存活率與著床率，
碎片>25%(C, D等級)之胚胎，胚葉blastomere不一致之胚胎，冷凍解凍之存活率較低

http://humrep.oxfordjournals.org/content/22/suppl_1/i9.full.pdf+html?ijkey=585c21253b2644a26b17a7d5cd20dfe24c87f97f&keytype2=tf_ipsecsha