染色體異常鑲嵌化嚴重程度與胚胎著床率有關
鑲嵌化越嚴重(>50%)著床率越低
鑲嵌化輕微(<50%)著床率類似正常胚胎

Fertil Steril. 2017 Nov 28. pii: S0015-0282(17)31958-1. doi: 10.1016/j.fertnstert.2017.09.025. [Epub ahead of print]

Extent of chromosomal mosaicism influences the clinical outcome of in vitro fertilization treatments.

Spinella F1, Fiorentino F2, Biricik A1, Bono S1, Ruberti A3, Cotroneo E1, Baldi M1, Cursio E3, Minasi MG3, Greco E3.

Author information

Abstract

OBJECTIVE:

To assess whether the extent of chromosomal mosaicism can influence the success rate of IVF treatments.

DESIGN:

Prospective study.

SETTING:

Private genetic and assisted reproduction centers.

PATIENT(S):

The transfer of mosaic embryos was offered to 77 women for which IVF resulted in no euploid embryos available for transfer.

INTERVENTION(S):

All embryos were cultured to blastocyst stage; trophectoderm biopsy was performed on day 5/6 of development. Comprehensive chromosome screening was performed using either next-generation sequencing or array-comparative genomic hybridization methodologies.

MAIN OUTCOME MEASURE(S):

The clinical outcome obtained after transfer of mosaic embryos with low (<50%) and high (≥50%) aneuploidy percentage was compared with that resulting from a control group of 251 euploid blastocysts.

RESULT(S):

A significantly higher implantation rate (48.9% vs. 24.2%), clinical pregnancy rate/ET (40.9% vs. 15.2%), and live-birth rate (42.2% vs. 15.2%) were observed comparing embryos with mosaicism <50% and ≥50%. Mosaic embryos with high aneuploidy percentage (≥50%) showed a significantly lower clinical pregnancy rate/ET (15.2% vs. 46.4%), implantation rate (24.4% vs. 54.6%), and live-birth rate (15.2% vs. 46.6%) than euploid blastocysts. In contrast, embryos with lower aneuploidy percentage (<50%) have a clinical outcome similar to euploid embryos.

CONCLUSION(S):

The results of this study further confirm that mosaic embryos can develop into healthy euploid newborns. We demonstrated that the extent of mosaicism influences the IVF success rate. Mosaic embryos with low aneuploidy percentage have higher chances of resulting in the birth of healthy babies compared with embryos with higher mosaicism levels.

IVF排卵針早上打針效果可能優於晚上打針

J Assist Reprod Genet. 2017 Dec 21. doi: 10.1007/s10815-017-1105-1. [Epub ahead of print]

A prospective, randomized study comparing morning to evening administration of gonadotropins in ART.

Sharara FI1,2, Mouhayar Y3, Goodwin M4, Abdo G4.

Author information

Abstract

OBJECTIVE:

We sought to determine whether administering the daily gonadotropin dose in the morning (AM) or in the evening (PM) affects cycle outcome in patients undergoing IVF.

DESIGN:

This is a prospective randomized study.

SETTING:

The study is performed in a private assisted reproductive technology (ART) clinic.

PATIENT(S):

The study included one hundred and twenty-seven women undergoing IVF.

INTERVENTION(S):

Morning (AM) and evening (PM) administration of gonadotropins (uFSH and hMG) was compared.

MAIN OUTCOME MEASURE(S):

Live birth rate was the main outcome measured. Secondary outcomes including total IU use, days of stimulation, peak E2, peak P4, endometrial thickness, number of oocytes retrieved, MII oocytes, fertilization rates, #ET, IR, and clinical PR were all assessed.

RESULTS:

A total of 127 cycles were included, 61 in the AM group and 67 in the PM group. Baseline and stimulation characteristics were similar in both groups. There was a trend for a higher implantation rate in the AM group vs. the PM group (60.3 vs. 47.2%, P = 0.066). The AM group had a higher chemical pregnancy rate compared to the PM group (81.7 vs. 65.6%, P = 0.024) and a higher clinical pregnancy rate (78.3 vs. 62.1%, P = 0.048), but the delivery rates were similar (68.3 vs. 56.1%, P = 0.16). The study was unfortunately prematurely terminated when uFSH (Bravelle©) was pulled out of the US market.

CONCLUSIONS:

AM administration of gonadotropins may be associated with a better ART outcome compared to PM administration. Larger studies are needed to confirm our findings.

Amphiregulin 用於不成熟卵子之IVM
可提高不成熟卵子正常減數分裂率49-->70%
D3胚胎率23--->43%;
囊胚率8--->18%

Hum Reprod. 2017 Oct 1;32(10):2056-2068. doi: 10.1093/humrep/dex262.

An improved IVM method for cumulus-oocyte complexes from small follicles in polycystic ovary syndrome patients enhances oocyte competence and embryo yield.

Sánchez F1, Lolicato F1, Romero S1,2, De Vos M1,3, Van Ranst H1, Verheyen G3, Anckaert E1, Smitz JEJ1.

Author information

Abstract

STUDY QUESTION:

Are meiotic and developmental competence of human oocytes from small (2-8 mm) antral follicles improved by applying an optimized IVM method involving a prematuration step in presence of C-Type Natriuretic Peptide (CNP) followed by a maturation step in presence of FSH and Amphiregulin (AREG)?

SUMMARY ANSWER:

A strategy involving prematuration culture (PMC) in the presence of CNP followed by IVM using FSH + AREG increases oocyte maturation potential leading to a higher availability of Day 3 embryos and good-quality blastocysts for single embryo transfer.

WHAT IS KNOWN ALREADY:

IVM is a minimal-stimulation ART with reduced hormone-related side effects and risks for the patients, but the approach is not widely used because of an efficiency gap compared to conventional ART. In vitro systems that enhance synchronization of nuclear and cytoplasmic maturation before the meiotic trigger are crucial to optimize human IVM systems. However, previous PMC attempts have failed in sustaining cumulus-oocyte connections throughout the culture period, which prohibited a normal cumulus-oocyte communication and precluded an adequate response by the cumulus-oocyte complex (COC) to the meiotic trigger.

STUDY DESIGN, SIZE, DURATION:

A first prospective study involved sibling oocytes from a group of 15 patients with polycystic ovary syndrome (PCOS) to evaluate effects of a new IVM culture method on oocyte nuclear maturation and their downstream developmental competence. A second prospective study in an additional series of 15 women with polycystic ovaries characterized and fine-tuned the culture conditions.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Fifteen women with PCOS (according to Rotterdam criteria) underwent IVM treatment after 3-5 days of highly purified human menopausal gonadotropin (HP-hMG) stimulation and no human chorionic gonadotropin (hCG) trigger before oocyte retrieval. A first study was designed with sibling oocytes to prospectively evaluate the impact of an IVM culture method: 24 h PMC with CNP + 30 h IVM with FSH and AREG, on embryo yield, in comparison to the standard (30 h) IVM clinical protocol (Group I, n = 15). A second prospective study was performed in 15 women with polycystic ovaries, to characterize and optimize the PMC conditions (Group II, n = 15). The latter study involved the evaluation of oocyte meiotic arrest, the preservation of cumulus-oocyte transzonal projections (TZPs), the patterns of oocyte chromatin configuration and cumulus cells apoptosis following the 24 and 46 h PMC. Furthermore, oocyte developmental potential following PMC (24 and 46 h) + IVM was also evaluated. The first 20 good-quality blastocysts from PMC followed by IVM were analysed by next generation sequencing to evaluate their aneuploidy rate.

MAIN RESULTS AND THE ROLE OF CHANCE:

PMC in presence of CNP followed by IVM using FSH and AREG increased the meiotic maturation rate per COC to 70%, which is significantly higher than routine standard IVM (49%; P ≤ 0.001). Hence, with the new system the proportion of COCs yielding transferable Day 3 embryos and good-quality blastocysts increased compared to routine standard IVM (from 23 to 43%; P ≤ 0.001 and from 8 to 18%; P ≤ 0.01, respectively). CNP was able to prevent meiosis resumption for up to 46 h. After PMC, COCs had preserved cumulus-oocyte TZPs. The blastocy

體重過胖減輕體重減少食量可提高懷孕率

Hum Reprod Update. 2017 Nov 1;23(6):681-705. doi: 10.1093/humupd/dmx027.

How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese? A systematic review and meta-analysis of the evidence.

Best D1, Avenell A2, Bhattacharya S1.

Author information

Abstract

BACKGROUND:

The prevalence of obesity is increasing worldwide, with a corresponding increase in overweight and obese patients referred with infertility. This systematic review aimed to determine whether non-surgical weight reduction strategies result in an improvement in reproductive parameters affected by obesity, e.g. delayed time to pregnancy, oligozoospermia and azoospermia. No prior reviews have examined this within the general fertility population, or in both sexes.

OBJECTIVE AND RATIONALE:

Our objective was to answer the question: 'In overweight and obese women, men and couples seeking fertility treatment, what non-surgical weight-loss interventions have been used, and how effective are they at weight loss and improving reproductive outcomes?'

SEARCH METHODS:

An electronic search of MEDLINE, EMBASE and the Cochrane Library was performed for studies between January 1966 and March 2016. Text word and MESH search terms used related to infertility, weight and barriers to weight loss. Inclusion criteria were an intervention to change lifestyle evaluated in any study design in participants of either gender with an unfulfilled desire to conceive. Studies were excluded if they included participants not attempting pregnancy, with illnesses that might cause weight fluctuations, or studies evaluating bariatric surgery. Two reviewers performed data extraction and quality assessment using the Cochrane Risk of Bias Tool for randomized trials, and a ratified checklist (ReBIP) for non-randomized studies.

OUTCOMES:

A total of 40 studies were included, of which 14 were randomised control trials. Primary outcomes were pregnancy, live birth rate and weight change. In women, reduced calorie diets and exercise interventions were more likely than control interventions to result in pregnancy [risk ratio 1.59, 95% CI (1.01, 2.50)], and interventions resulted in weight loss and ovulation improvement, where reported. Miscarriage rates were not reduced by any intervention.

無精症病患染色體異常率約15%
其中大部分賀爾蒙FSH, LH均上升
最常見之染色體異常為 Klinefelter syndrome
 Klinefelter syndrome染色體異常睪丸取精取得率約28%

Hum Reprod. 2017 Dec 1;32(12):2574-2580. doi: 10.1093/humrep/dex307.

Chromosomal abnormalities in 1663 infertile men with azoospermia: the clinical consequences.

Donker RB1, Vloeberghs V2, Groen H3, Tournaye H2, van Ravenswaaij-Arts CMA4, Land JA1.

Author information

Abstract

STUDY QUESTION:

What is the prevalence of chromosomal abnormalities in azoospermic men and what are the clinical consequences in terms of increased risk for absent spermatogenesis, miscarriages and offspring with congenital malformations?

SUMMARY ANSWER:

The prevalence of chromosomal abnormalities in azoospermia was 14.4%, and the number of azoospermic men needed to be screened (NNS) to identify one man with a chromosomal abnormality with increased risk for absence of spermatogenesis was 72, to prevent one miscarriage 370-739 and to prevent one child with congenital malformations 4751-23 757.

WHAT IS KNOWN ALREADY:

Infertility guidelines worldwide advise screening of non-iatrogenic azoospermic men for chromosomal abnormalities, but only few data are available on the clinical consequences of this screening strategy.

STUDY DESIGN, SIZE, DURATION:

This retrospective multicentre cross-sectional study of non-iatrogenic azoospermic men was performed at the University Hospital Brussels, Belgium, and the University Medical Centre Groningen, The Netherlands, between January 2000 and July 2016.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Analysis of clinical registries retrospectively identified 1663 non-iatrogenic azoospermic men with available results of karyotyping and FSH serum levels. Iatrogenic azoospermia was an exclusion criterion, defined as azoospermia after spermatotoxic medical treatment, exogenous androgen suppletion or vasectomy and/or vasovasostomy. Also, men with a clinical diagnosis of anejaculation or hypogonadotropic hypo-androgenism and/or FSH values <1.0 U/l were excluded. Chromosomal abnormalities were categorized according to their (theoretical) impact on clinical consequences for the patient (i.e. an increased risk for absence of spermatogenesis) and adverse pregnancy outcomes (i.e. miscarriage or offspring with congenital malformations), in both normogonadotropic (FSH < 10 U/l) and hypergonadotropic (FSH ≥ 10 U/l) azoospermia. We estimated the NNS for chromosomal abnormalities to identify one man with absence of spermatogenesis and to prevent one miscarriage or one child with congenital malformations, and calculated the surgical sperm retrieval rates per chromosomal abnormality.

MAIN RESULTS AND THE ROLE OF CHANCE:

The overall prevalence of chromosomal abnormalities in azoospermia was 14.4% (95% CI 12.7-16.1%), its prevalence being higher in hypergonadotropic azoospermia (20.2%, 95% CI 17.8-22.7%) compared to normogonadotropic azoospermia (4.9%, 95% CI 3.2-6.6%, P < 0.001). Klinefelter syndrome accounted for 83% (95% CI 77-87%) of abnormalities in hypergonadotropic azoospermia. The NNS to identify one man with increased risk for absence of spermatogenesis was 72, to prevent one miscarriage 370-739, and to prevent one child with congenital malformations 4751-23 757. There was no clinically significant difference in NNS between men with normogonadotropic and hypergonadotropic azoospermia. The surgical sperm retrieval rate was significantly higher in azoospermic men with a normal karyotype (60%, 95% CI 57.7-63.1%) compared to men with a chromosomal abnormality (32%, 95% CI 25.9-39.0%, P < 0.001). The sperm retrieval rate in Klinefelter syndrome was 28% (95% CI 20.7-35.0%).

切掉單一邊卵巢，易造成日後IVF 卵子數量下降，活產率會明顯下降 30%

Hum Reprod. 2017 Dec 4:1-10. doi: 10.1093/humrep/dex358. [Epub ahead of print]

Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy: results of a multicentre cohort study.

Lind T1,2, Holte J3,4, Olofsson JI5,6, Hadziosmanovic N7, Gudmundsson J8, Nedstrand E9, Lood M10, Berglund L7, Rodriguez-Wallberg K6,11.

Author information

Abstract

STUDY QUESTION:

Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)?

SUMMARY ANSWER:

A significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos.

WHAT IS KNOWN ALREADY:

Similar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO.

STUDY DESIGN, SIZE, DURATION:

This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linné Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linköping University Hospital (D) and Örebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments.

MAIN RESULTS AND THE ROLE OF CHANCE:

The exposed (UO) and control women's groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P = <0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = <0.001, respectively).