2016年7月25日

取卵過程中,卵泡是空泡(取不到卵子)比率越高,卵子受孕率&胚胎分裂率越低,懷孕率越低

 2016 Jul-Sep;10(2):169-74. Epub 2016 Jun 1.

Use of Follicular Output Rate to Predict Intracytoplasmic Sperm Injection Outcome.

Abstract

BACKGROUND:

The measurement of follicular output rate (FORT) has been proposed as a good indicator for evaluating follicular response to the exogenous recombinant folliclestimulating hormone (rFSH). This places FORT as a promising qualitative marker for ovarian function. The objective of the study was to determine FORT as a predictor of oocyte competence, embryo quality and clinical pregnancy after intracytoplasmic sperm injection (ICSI).

MATERIALS AND METHODS:

This prospective study was carried out on a group of infer- tile females (n=282) at Islamabad Clinic Serving Infertile Couples, Islamabad, Pakistan, from June 2010 till August 2013. Downregulated females were stimulated in injection gonadotropins and on ovulation induction day, pre-ovulatory follicle count (PFC) was determined using transvaginal ultrasound scan (TVUS), and FORT was determined as a ratio of PFC to antral follicle count (AFC)×100. Group I consisted of females with a negative pregnancy test, while group II had a positive pregnancy test that was confirmed with the appearance of fetal cardiac activity. Linear regression analyses of categorical variables of clinical pregnancy along with other independent variables, including FORT, were performed using SPSS version 15.0.

RESULTS:

Pregnancy occurred in 101/282 women who were tested, recording a clinical pregnancy rate of about 35.8%. FORT values were higher in group II as compared to group I females (P=0.0001). In multiple regression analysis, 97.7, 87.1, 78.2, and 83.4% variations were explained based on the number of retrieved oocytes per patients, number of metaphase II oocytes retrieved, number of fertilized oocytes, and number of cleaved embryos, respectively, indicating FORT as an independent predictor.

CONCLUSION:

FORT is a predictor of oocyte competence in terms of a number of retrieved, mature and fertilized oocytes. It also gives information about the number of cleaved embryos and clinical pregnancy rate.

2016年7月23日

動物研究顯示,魚油補充可能可提高精蟲品質(數量, 活動力)


 2016 Jul-Sep;10(2):223-31. Epub 2016 Jun 1.

Effect of Long-Term Fish Oil Supplementation on Semen Quality and Serum Testosterone Concentrations in Male Dogs.

Abstract

BACKGROUND:

Manipulating the dietary fatty acid (FA) content can alter FA profiles of reproductive tissues. Numerous researchers have evaluated the effect of fish oil (FO) supplementation on reproductive characteristics in domestic animals, but reliable information concerning dietary FO effects on semen quality and testosterone concentrations in dogs has not been reported. Therefore, this study evaluated the effects of dietary FO on semen quality and serum testosterone concentrations in dogs.

MATERIALS AND METHODS:

In this cross-over experimental study, 5 male dogs consumed either a control diet or the same diet supplemented with 54 mg FO/kg metabolic body weight (BW) for 120 days. After the 120-day wash-out period, control (C) dogs received FO and FO-fed dogs consumed the control diet. In the first period, 2 dogs were allocated to the FO group and 3 to the C group. In the second period, 3 dogs were allocated to the FO group and 2 to the C group. Semen samples collected on days 0, 60, 90 and 120 were evaluated by standard methods. Day 120 semen samples were analyzed for FA profiles. Blood samples were collected on days 0, 30, 60, 90 and 120 to measure serum testosterone concentrations. Data were analyzed by analysis of variance with repeated measures using the Mixed Models procedure of SAS (version 9.0, SAS Institute Inc., Cary, NC, USA). Animals and period of time (first or second 120 days) were random variables; and treatment, time, and the treatment by time interaction were considered fixed effects.

RESULTS:

FO supplementation increased the percentage of motile sperm (P=0.02), total sperm count (P<0.01), total sperm viability (P<0.01), and total morphologically normal sperm (P<0.01). Supplementation decreased the percentage of viable sperm (P=0.03) and serum testosterone concentration (P<0.01). FO supplementation also increased the percentage of arachidonic acid, eicosapentaenoic acid, (EPA) and total n-3 in semen samples (P≤0.05).

CONCLUSION:

These results are consistent with the concept that long-term FO supplementation influences semen quality and testosterone concentrations in dogs by altering semen FA profiles.

2016年7月19日

動物研究顯示全卵玻璃化冷凍可行性:   將母羊全卵切除後以玻璃化冷凍在解凍後血管重接後,卵巢保存局部生殖功能(原始卵泡存活率0.3%)


 2016 Jun 22. [Epub ahead of print]

Safeguarding Fertility With Whole Ovary Cryopreservation and Microvascular Transplantation: Higher Follicular Survival With Vitrification Than With Slow Freezing in a Ewe Model.

Abstract

BACKGROUND:

In young women, ovarian cortex cryopreservation before gonadotoxic chemotherapy and its avascular grafting after cancer healing permitted fertility restoration. However, ischemia reduced the grafts' lifespan. Microvascular transplantation of cryopreserved whole ovary may allow immediate revascularization, ensuring better fertility preservation, but the best cryopreservation method is unknown. We aimed to compare slow freezing and vitrification of whole ovary for fertility preservation purposes, in an ewe model.

METHODS:

Twelve ewes were allocated at random to slow freezing (n = 6) or vitrification group (n = 6). Ewes' left ovary was removed and cryopreserved. Dimethyl sulfoxide 2 M was used as cryoprotector for slow freezing. Vitrification was obtained using increasing concentrations of avitrification solution of the latest generation (VM3) and gradual temperature lowering to minimize toxicity. After a month, the right ovary was removed, the left ovary was thawed/warmed, and its vessels were anastomosed to the right pedicle. Fertility and ovarian function were assessed for 3 years. Ovarian follicles in native and transplanted ovaries were counted and compared at study completion.

RESULTS:

Hormonal secretion resumed in all ewes of both groups. One ewe of the slow-freezing group delivered healthy twins 1 year 9 months and 12 days after transplantation. Estimated whole follicle survival was very low in both groups but significantly higher after vitrification than after slow freezing (0.3% ± 0.5% vs 0.017% ± 0.019%, respectively; p < 0.05).

CONCLUSIONS:

Further progress is needed before whole-ovary cryopreservation can be considered an option for safeguarding fertility. Whole ovary vitrification provides better follicular survival compared to slow freezing and may be a valuable cryopreservation option.
COH後之不成熟卵M1 冷凍存活率與成熟卵M2 冷凍存活率類似  (81.1%  vs 85.2%)
未經COH之不成熟卵M1 冷凍後胚胎成熟至M2率遠低於成熟卵M2  (39.1 vs 73.3%)


 2016 Jul 12. [Epub ahead of print]

Should metaphase 1 and 2 stages oocytes be vitrified in the same time for fertility preservation?

Abstract

AIMS:

Could metaphase 1 (M1) and 2 (M2) stages oocytes from in vitro maturation (IVM) cycles and controlled-ovarian hyperstimulation (COH) cycles be frozen at the same time without any adverse effect of vitrification on further survival (SR) and maturation rates (MR)?

MATERIALS & METHODS:

M1 from cancer patients were prospectively included in IVM/COH groups, and in study or control subgroups if they were vitrified or not. In each study subgroup, SR were compared with that of M2 oocytes vitrified/warmed from egg donors. MR were compared with those of fresh-M1 oocytes from control IVM/COH subgroups.

RESULTS:

SR were not different between groups. MR compared respectively between survived- and fresh-M1 oocytes were similar when resulting from COH (85.2 vs 81.1%) but significantly lower after IVM (39.1 vs 73.3%).

CONCLUSION:

Simultaneous freezing of M1/M2 oocytes could be applied to COH but not to IVM during the course of fertility preservation.

2016年7月9日

施打FSH可改善男性精蟲DNA異常
(150 IU recombinant human FSH s.c. every other day for 12 weeks)

 2016 Jun 20. pii: dew167. [Epub ahead of print]

Treatment with human, recombinant FSH improves sperm DNA fragmentation in idiopathic infertile men depending on the FSH receptor polymorphism p.N680S: a pharmacogenetic study.

Abstract

STUDY QUESTION:

Does the sperm DNA fragmentation index (DFI) improve depending on the FSH receptor (FSHR) genotype as assessed by the nonsynonymous polymorphisms rs6166 (p.N680S) after 3 months of recombinant FSH treatment in men with idiopathic infertility?

SUMMARY ANSWER:

FSH treatment significantly improves sperm DFI only in idiopathic infertile men with the p.N680S homozygous N FSHR.

WHAT IS KNOWN ALREADY:

FSH, fundamental for spermatogenesis, is empirically used to treat male idiopathic infertility and several studies suggest that DFI could be a candidate predictor of response to FSH treatment, in terms of probability to conceive. Furthermore, it is known that the FSHR single nucleotide polymorphism (SNP) rs6166 (p.N680S) influences ovarian response in women and testicular volume in men.

STUDY DESIGN, SIZE AND DURATION:

A multicenter, longitudinal, prospective, open-label, two-arm clinical trial was performed. Subjects enrolled were idiopathic infertile men who received 150 IU recombinant human FSH s.c. every other day for 12 weeks and were followed-up for a further 12 weeks after FSH withdrawal. Patients were evaluated at baseline, at the end of treatment and at the end of follow-up.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Eighty-nine men with idiopathic infertility carrier of the FSHR p.N680S homozygous N or S genotype, FSH ≤ 8 IU/l and DFI >15%, were enrolled. A total of 66 patients had DFI analysis completed on at least two visits. DFI was evaluated in one laboratory by TUNEL/PI (propidium iodide) assay coupled to flow cytometry, resolving two different fractions of sperm, namely the 'brighter' and 'dimmer' sperm DFI fractions.

MAIN RESULTS AND THE ROLE OF CHANCE:

Thirty-eight men (57.6%) were carriers of the p.N680S homozygous N and 28 (42.4%) of the homozygous S FSHR. Sperm concentration/number was highly heterogeneous and both groups included men ranging from severe oligozoospermia to normozoospermia. Total DFI was significantly lower at the end of the study in homozygous carriers of the p.N680S N versus p.N680S S allele (P = 0.008). Total DFI decreased significantly from baseline to the end of the study (P = 0.021) only in carriers of the p.N680S homozygous N polymorphism, and this decrease involved the sperm population containing vital sperm (i.e. brighter sperm) (P = 0.008). The dimmer sperm DFI fraction, including only nonvital sperm, was significantly larger in p.N680S S homozygous patients than in homozygous N men (P = 0.018). Total DFI was inversely related to total sperm number (P = 0.020) and progressive sperm motility (P = 0.014). When patients were further stratified according to sperm concentration (normoozospermic versus oligozoospermic) or -211G>T polymorphism in the FSHB gene (rs10835638) (homozygous G versus others), the significant improvement of sperm DFI in FSHR p.N680S homozygous N men was independent of sperm concentration and associated with the homozygous FSHB -211G>T homozygous G genotype.
PGD可大幅提高囊胚之著床率(63.2% vs. 26.2%)


 2016 Apr-Jun;9(2):94-100. doi: 10.4103/0974-1208.183512.

Preimplantation genetic screening for all 24 chromosomes by microarray comparative genomic hybridization significantly increases implantation rates and clinical pregnancy rates in patients undergoing in vitro fertilization with poor prognosis.

Abstract

CONTEXT:

A majority of human embryos produced in vitro are aneuploid, especially in couples undergoing in vitro fertilization (IVF) with poor prognosis. Preimplantation genetic screening (PGS) for all 24 chromosomes has the potential to select the most euploid embryos for transfer in such cases.

AIM:

To study the efficacy of PGS for all 24 chromosomes by microarray comparative genomic hybridization (array CGH) in Indian couples undergoing IVF cycles with poor prognosis.

SETTINGS AND DESIGN:

A retrospective, case-control study was undertaken in an institution-based tertiary care IVF center to compare the clinical outcomes of twenty patients, who underwent 21 PGS cycles with poor prognosis, with 128 non-PGS patients in the control group, with the same inclusion criterion as for the PGS group.

MATERIALS AND METHODS:

Single cells were obtained by laser-assisted embryo biopsy from day 3 embryos and subsequently analyzed by array CGH for all 24 chromosomes. Once the array CGH results were available on the morning of day 5, only chromosomally normal embryos that had progressed to blastocyst stage were transferred.

RESULTS:

The implantation rate and clinical pregnancy rate (PR) per transfer were found to be significantly higher in the PGS group than in the control group (63.2% vs. 26.2%, P = 0.001 and 73.3% vs. 36.7%, P = 0.006, respectively), while the multiple PRs sharply declined from 31.9% to 9.1% in the PGS group.

CONCLUSIONS:

In this pilot study, we have shown that PGS by array CGH can improve the clinical outcome in patients undergoing IVF with poor prognosis.
子宮肌瘤切除後子宮腔沾黏機率提高,
不論肌瘤種類數量大小,子宮腔沾黏機率提高達2成 [11 out of 51 (21.57%) cases.]


 2016 Apr-Jun;9(2):107-11. doi: 10.4103/0974-1208.183509.

Effect of myomectomy on endometrial cavity: A prospective study of 51 cases.

Abstract

CONTEXT:

Fibroids are the most common tumors of the uterine cavity. Most of them are diagnosed during the reproductive age when the fertility is an important concern for the female. However, complications can occur after removal of fibroid (myomectomy) too for future pregnancy. Though myomectomy has been sighted as a cause of intrauterine adhesions data regarding the effect of myomectomy on endometrial cavity is lacking.

AIMS:

Evaluate the incidence of intrauterine adhesion formation after myomectomy and to identify the associated factors.

MATERIALS AND METHODS:

In this prospective observational study, hysteroscopy was done in 51 infertile patients who had undergone myomectomy 3 months before in a tertiary care center from 2012 to 2015. The presence of intrauterine adhesions noted on hysteroscopy was investigated on the basis of size, number, location and type of fibroid removed, along with intraoperative breach of the uterine cavity.

STATISTICAL ANALYSIS:

Chi-square test was used for the calculating significant difference in frequency of discrete variables in two groups. P < 0.05 was considered significant.

RESULTS:

Intrauterine adhesions were seen in 11 out of 51 (21.57%) cases. No significant relationship between intrauterine adhesions and type, size or number of fibroid was observed. No statistical difference in the rate of adhesion formation was seen irrespective of breach of the uterine cavity during myomectomy.

CONCLUSION:

Intrauterine adhesion formation after myomectomy is not related to the type of surgery or the nature of fibroid. However, in all cases desiring fertility postoperative hysteroscopy is highly recommended to diagnose and treat these adhesions early.

2016年7月6日

阻塞性無精症應使用較無侵犯性之經皮睪丸取精Percutaneous testicular sperm aspiration (TESA, 取精率達100%
非阻塞性無精症應使用TESA取精, 取精率達30%
PESA (經皮副睪取精) or TESA應採為無精症取精之第一線治療(而非睪丸切片取精)


 2016 Mar;4(2):257-62. doi: 10.1111/andr.12143. Epub 2016 Jan 20.

Multiple needle-pass percutaneous testicular sperm aspiration as first-line treatment in azoospermic men.

Jensen CF1,2,3Ohl DA1Hiner MR4Fode M2Shah T4Smith GD1,4Sonksen J2,3.

Abstract

Percutaneous testicular sperm aspiration (TESA) has been known for decades as a simple, minimally invasive approach to sperm retrieval in azoospermic men. Because of lower reported sperm retrieval rates (SRR) when compared with microdissection testicular sperm extraction (mTESE), many centers now use mTESE as the first choice for retrieving spermatozoa in nonobstructive azoospermia (NOA). Objectives of this study were to evaluate the outcome and safety of TESA and mTESE in the treatment of azoospermia and to investigate the usefulness of a prognostic TESA to individualize protocols for couples and limit the use of invasive testicular procedures. IRB approval was obtained to retrospectively evaluate 208 patients undergoing multiple needle-pass TESA between 1999 and 2014. Prognostic TESA was performed on 125 men with NOA and 82 with obstructive azoospermia (OA). Nine NOA men and 31 OA men with previously demonstrated spermatozoa had a subsequent therapeutic TESA while nine NOA men with a failed TESA proceeded to mTESE. Main outcome measures were complication rates and SRR. SRR of the prognostic TESA was 30% (38/125) for NOA men and 100% (82/82) for OA men. Eight/nine NOA men and 31/31 OA men had spermatozoa found for intracytoplasmic sperm injection in a subsequent therapeutic TESA. In nine NOA men in whom a TESA produced no spermatozoa, only one had spermatozoa found with mTESE. Overall complication rates of TESA and mTESE were 3% (7/267) and 21% (3/14), respectively. TESA provides reasonable SRR and is a safe procedure. Successful prognostic TESA indicates future success with therapeuticTESA. Men with a failed TESA have a limited chance of sperm retrieval using mTESE. Approaching azoospermic men with an initial prognosticTESA followed by either therapeutic TESA and/or mTESE is an efficient algorithm in the management of azoospermia and limits the use of more invasive procedures.

2016年7月5日

berberine黃連 對多囊性卵巢PCO無明顯助益


 2016 Jun 20. pii: S0015-0282(16)61289-X. doi: 10.1016/j.fertnstert.2016.05.022. [Epub ahead of print]

Randomized controlled trial of letrozole, berberine, or a combination for infertility in the polycystic ovary syndrome.

Abstract

OBJECTIVE:

To study whether a combination of berberine and letrozole results in higher live births than letrozole alone in infertile women with polycystic ovary syndrome (PCOS).

DESIGN:

A multicenter randomized double-blinded placebo-controlled trial.

SETTING:

Reproductive and developmental network sites.

PATIENT(S):

Eligible women had PCOS as defined by the Rotterdam criteria. We enrolled 644 participants randomized 1:1:1 among letrozole, berberine, and combination groups.

INTERVENTIONS(S):

Berberine or berberine placebo were administrated orally at a daily dose of 1.5 g for up to 6 months. Patients received an initial dose of 2.5 mg letrozole or placebo on days 3-7 of the first three treatment cycles. This dose was increased to 5 mg on the last three cycles if not pregnant.

MAIN OUTCOMES MEASURE(S):

Cumulative live births.

RESULTS:

The cumulative live births were similar between the letrozole and combination groups after treatment (36% and 34%), and were superior to those in the berberine group (22%). Likely, conception, pregnancy, and ovulation rates were similar between the letrozole and combination groups, and these were significantly higher than in the berberine group. There was one twin birth in the letrozole group, three twin births in the combination group, and none in the berberine group.

CONCLUSION(S):

Berberine did not add fecundity in PCOS when used in combination with the new ovulation agent letrozole.
不成熟卵子(GV, MI)
細胞質較黏稠, 細胞膜及ZP較高彈性, ICSI較不易穿刺, 漏斗形成時間持續較短(立即消失)
(GV比MI更明顯)

 2016 Jun 20. pii: S0015-0282(16)61344-4. doi: 10.1016/j.fertnstert.2016.06.015. [Epub ahead of print]

Characterization of the injection funnel during intracytoplasmic sperm injection reflects cytoplasmic maturity of the oocyte.

Abstract

OBJECTIVE:

To quantify cytoplasmic maturity on the basis of intracytoplasmic sperm injection (ICSI) injection funnel manifestation and to evaluate influence factors of the latter.

DESIGN:

Prospective study.

SETTING:

Private fertility center.

PATIENT(S):

A total of 31 patients with good ovarian response.

INTERVENTION(S):

Mature and immature oocytes were injected intracytoplasmatically. Formation and persistence of an injection funnel was documented and measured.

MAIN OUTCOME MEASURE(S):

ICSI funnel size, persistence of injection funnel, rates of degeneration and fertilization, embryo quality.

RESULT(S):

Funnel volume in germinal vesicle stage oocytes (prophase I [PI]) was significantly smaller than that of metaphase I (MI) and MII oocytes. Immature eggs (PI, MI) almost never showed a persistent funnel 2-4 minutes after ICSI, whereas in MII eggs the funnel was still observable in 35% (117/334) of the cases. Uni- and multivariate analysis revealed that pipette type and stimulation protocol significantly influenced appearance of injection funnel. Funnel volume in oocytes that fertilized regularly was significantly higher compared with three-polar body and degenerated oocytes.

CONCLUSION(S):

Oocyte maturation within the follicle is closely associated with a remarkable change in cytoplasm viscosity from an aqueous to a more viscous subtype. Precise evaluation of the injection funnel may help to explain deviations from expected ICSI outcome and could also assist in optimizing controlled ovarian hyperstimulation.

2016年7月4日

卵巢早衰(38 years, FSH>10, AMH<1), 胚胎染色體異常率提高
PGD顯示胚胎染色體正常, 不論其母體卵巢功能是否下降, 移植後著床率無明顯差異


 2016 Jun 28. pii: S0015-0282(16)61345-6. doi: 10.1016/j.fertnstert.2016.06.016. [Epub ahead of print]

Higher rates of aneuploidy in blastocysts and higher risk of no embryo transfer in recurrent pregnancy loss patients with diminished ovarian reserve undergoing in vitro fertilization.

Abstract

OBJECTIVE:

To study the prediction of aneuploidy rate in blastocysts from patients with recurrent pregnancy loss (RPL) on the basis of ovarian reserve testing.

DESIGN:

Prospective cohort analysis.

SETTING:

Private, university-affiliated fertility clinic.

PATIENT(S):

A total of 239 patients with RPL, defined as two or more clinical miscarriages, were screened for inclusion. One hundred two (102) cycles in patients with unexplained RPL resulted in at least one euploid embryo transferred. Outcomes were compared by ovarian reserve test results, with diminished ovarian reserve (DOR) defined as a cycle day 3 FSH >10 IU/mL and/or antimüllerian hormone <1 ng/mL.

INTERVENTION(S):

In vitro fertilization with blastocyst biopsy and aneuploidy screening of all 23 chromosome pairs.

MAIN OUTCOME MEASURE(S):

Rate of aneuploidy in blastocysts and incidence of IVF cycles with no transfer owing to no euploid blasts.

RESULT(S):

Patients with DOR had a higher percentage of aneuploid blastocysts (57% vs 49%) and a higher incidence of no euploid embryos to transfer (25% vs 13%). The higher rate of aneuploidy in blastocysts was most significant in patients aged <38 years (67% vs 53%). Implantation rates after transfer of euploid blastocysts were similar (61% compared with 59%), and miscarriage rates were low (14% and 10%).

CONCLUSION(S):

Unexplained RPL patients with DOR have a higher percentage of aneuploid blastocysts and risk of no euploid embryo to transfer compared with unexplained RPL patients with normal ovarian reserve testing. The difference is most significant in patients aged <38 years. Patients with RPL and DOR with euploid embryo transferred had similar outcomes compared with patients with RPL and normal ovarian reserve testing.

2016年7月3日

IVF使用GnRHantagonist抑制自發性排卵失敗率約1.6%, 好發於FSH較高卵巢功能較差病患
IVF使用GnRHagonist抑制自發性排卵失敗率約0.15%


 2016 May 25;51(5):352-6. doi: 10.3760/cma.j.issn.0529-567X.2016.05.006.

[Spontaneous ovulation in in vitro fertilization-embryo transfer cycles usinggonadotropin-releasing hormone antagonist: a large-sample retrospective study].

[Article in Chinese]

Abstract

OBJECTIVE:

To investigate the premature spontaneous ovulation rates in in vitro fertilization-embryo transfer (IVF-ET) cycles using gonadotropin-releasing hormone antagonist (GnRH-ant) and gonadotropin-releasing hormoneagonist (GnRH-a), as well as the risk factors for premature spontaneous ovulation.

METHODS:

The rates of premature spontaneous ovulation in a total of 10 612 cycles using GnRH-ant or GnRH-a were compared. Matched case-controlled study and binary logistic regression model were conducted to analyze the risk factors for premature spontaneous ovulation.

RESULTS:

The spontaneous ovulation rate in the whole for GnRH-a cycles was 0.15% (13/8 514), compared with a 1.62% (34/2 098) in GnRH-ant cycles (P<0.01). Further matched controlled study and regression analyze found out that higher basal FSH level was a predominant risk and prediction factor for spontaneous ovulation (OR=1.20, P=0.009).

CONCLUSIONS:

In GnRH-ant cycles, spontaneous ovulation rate is about 10 times than which in GnRH-a cycles. Diminished ovarian function is a predominate risk factor for premature spontaneous ovulation.