男性賀爾蒙過低之不明原因不孕症   常常合併精蟲品質較差 &懷孕率較低

Fertil Steril. 2019 Apr 11. pii: S0015-0282(19)30075-5. doi: 10.1016/j.fertnstert.2019.01.034. [Epub ahead of print]

Association between testosterone, semen parameters, and live birth in men with unexplained infertility in an intrauterine insemination population.

Trussell JC1, Coward RM2, Santoro N3, Stetter C4, Kunselman A4, Diamond MP5, Hansen KR6, Krawetz SA7, Legro RS8, Heisenleder D9, Smith J10, Steiner A11, Wild R6, Casson P12, Coutifaris C13, Alvero RR14, Robinson RB15, Christman G16, Patrizio P17, Zhang H18, Lindgren MC19; Reproductive Medicine Network.

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Abstract

OBJECTIVE:

To determine whether men with unexplained infertility and low total T (TT) have abnormal spermatogenesis and lower fecundity.

DESIGN:

Secondary analysis of the prospective, randomized, multicenter clinical trial, Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS).

SETTING:

Reproductive Medicine Network infertility clinics.

PATIENT(S):

Nine hundred couples with unexplained infertility enrolled in AMIGOS. Semen analysis with an ejaculate of at least 5 million total motile sperm was required for enrollment. For inclusion in this secondary analysis, a fasting TT was required.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Logistic regression, adjusted for age and body mass index, assessed the association between low TT (defined as <264 ng/dL), semen parameters, and pregnancy outcome.

RESULT(S):

Seven hundred eighty-one men (mean age, 34.2 ± 5.7 years) with a median (interquartile range) TT of 411 (318-520) ng/dL were included. Men with TT <264 ng/dL were less likely to have normal (≥4% strict Kruger) morphology (unadjusted odds ratio [OR], 0.56; 95% confidence interval [CI], 0.34, 0.92; adjusted OR, 0.59; 95% CI, 0.35, 0.99). There was no association between low TT and semen volume < 1.5 mL, sperm concentration < 15 × 106/mL, or motility < 40%. Among couples whose male partner had low TT, 21 (18.8%) had a live birth, compared with 184 (27.5%) live births in couples with a male partner having TT > 264 ng/dL. The odds of live birth decreased by 40% in couples whose male partner had low TT (unadjusted OR, 0.60; 95% CI, 0.36, 1.00; adjusted OR, 0.65; 95% CI, 0.38, 1.12).

CONCLUSION(S):

In couples with unexplained infertility, low TT in the male partner was associated with abnormal sperm morphology and lower live birth rates.

4細胞時期支胚葉細胞對稱方式與胚胎品質與囊胚形成率&懷孕有絕對相關姓
Tetrahedral (TET) 優於  nontetrahedral embryos

Fertil Steril. 2019 Apr 11. pii: S0015-0282(19)30130-X. doi: 10.1016/j.fertnstert.2019.02.019. [Epub ahead of print]

Blastomere cleavage plane orientation and the tetrahedral formation are associated with increased probability of a good-quality blastocyst for cryopreservation or transfer: a time-lapse study.

Desai N1, Gill P2.

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Abstract

OBJECTIVE:

To determine whether blastomere spatial arrangement in early human embryos is reflective of embryonic potential.

DESIGN:

Retrospective analysis of prospectively collected data.

SETTING:

Single academic center.

PATIENT(S):

Patients undergoing a single blastocyst transfer.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Developmental kinetics, blastocyst quality, embryo dysmorphisms, and live birth rate.

RESULT(S):

A total of 716 embryos were examined in detail for cleavage plane orientation, blastomere arrangement, and morphokinetic behavior. Tetrahedral (TET) and nontetrahedral embryos (nTET) differed significantly in developmental kinetics. The frequency of dysmorphisms, multinucleation, and irregular chaotic division was higher in nTET embryos. Only 44% of nTET versus 62.9% of TET embryos were scored as top-quality blastocysts. After adjusting for age, our data indicated that having TET embryos significantly increased the odds of having a blastocyst for cryopreservation/transfer (odds ratio, 3.58; confidence interval, 2.42-5.28) when compared with nTET. A total of 164 fresh single ETs were performed with blastocyst-stage embryos. The implantation rate for TET- and nTET-derived blastocysts were similar (64.7% and 62%, respectively). The live birth rate was 55% in both groups. A meridonal first division was noted in 85% of the fresh SET blastocysts.

CONCLUSION(S):

Cleavage plane orientation during the first three divisions appeared to dictate final blastomere spatial arrangement. The TET formation at the four-cell stage was predictive for embryos most likely to develop into good-quality blastocysts for cryopreservation/transfer. Morphokinetic markers of embryo potential were significantly different between TET and nTET embryos.

癌症化療(Cisplatin, cyclophosphamide)直接造成原始濾泡細胞衰老死亡

Mol Hum Reprod. 2019 Apr 6. pii: gaz020. doi: 10.1093/molehr/gaz020. [Epub ahead of print]

Cisplatin- and cyclophosphamide-induced primordial follicle depletion is caused by direct damage to oocytes.

Nguyen QN1,2, Zerafa N2, Liew SH2, Findlay JK1,3, Hickey M1,4, Hutt KJ2.

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Abstract

It is well established that DNA-damaging chemotherapies can cause infertility and ovarian endocrine failure by depleting the ovarian reserve of primordial follicles. Currently, no effective pharmacological therapies exist for the preservation of long-term fertility and ovarian function in female cancer patients, due to a limited understanding of the mechanisms of chemotherapy-induced follicle depletion. This study investigated the cellular targets, molecular mechanisms, and temporal course of ovarian reserve depletion following treatment with commonly used chemotherapeutic drugs. Adult female C57BL/6 mice were injected i.p. with saline, cisplatin (5mg/kg), or cyclophosphamide (300mg/kg); ovaries were harvested after 8 or 24 hours. Follicle counts showed depletion of all follicular stages 24 hours after administration of cisplatin or cyclophosphamide. Eight hours post-treatment, H2A histone family member X (γH2AX) immunofluorescence showed DNA double-stranded breaks at all follicular stages, including within primordial follicle oocytes. This staining was resolving by 24 hours, indicating that primordial follicle oocytes begin to undergo either apoptosis or repair in this timeframe. γH2AX-positive follicles were further examined to identify the specific cell types damaged. In primordial, transitional, and primary follicles, only oocytes sustained DNA damage, whereas in secondary and antral follicles, only somatic cells were affected. TUNEL staining confirmed that apoptosis occurs in these targeted cell types. Whilst multi-drug and multi-dose regimens were not examined, this study conclusively shows that cyclophosphamide and cisplatin cause direct damage to primordial follicle oocytes, which then undergo apoptosis. Therefo

大部分(78%) 均等大小之3細胞胚胎之染色體是異常狀態 ( 第1, 16, and 18 followed by 13, 19, and 21對染色體異常)

J Assist Reprod Genet. 2019 Feb;36(2):307-314. doi: 10.1007/s10815-018-1362-7. Epub 2018 Nov 16.

Chromosome constitution of equal-sized three-cell embryos using next-generation sequencing technology.

Ma M1, Zhang S1, Lu C1, Wang S1, Yao Y1, Peng H2.

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Abstract

PURPOSE:

To study the chromosome constitution of equal-sized three-cell embryo.

METHODS:

We determined the chromosome constitution of 105 blastomeres from 35 embryos using multiple annealing and looping-based amplification cycles (MALBAC) together with NGS sequencing technology. Chromosomal copy number variation (CNV) analysis was successfully performed in 27 embryos. We also analyzed radius, perimeter, area, and volume of each blastomere to explore the possibility of selecting the normal embryos.

RESULTS:

Majority of the embryos (77.8%, 21/27) studied were mosaic or aneuploid, and only 22.2% (6/27) had normal chromosome numbers. The aneuploid chromosomes spread across all chromosomes and the most frequent aneuploidies were for chromosomes 1, 16, and 18 followed by 13, 19, and 21. Statistical analyses showed no significant difference between euploid and aneuploid embryos regarding radius, perimeter, area, and volume of their blastomeres.

CONCLUSIONS:

Our results showed that majority of the equal-sized three-cell embryos were chromosomally abnormal and could not be distinguished by morphology observation, so they should be given lower priority at selection for transfer.

多囊性卵巢PCO胚胎染色體異常率較一般病人高 (61.3% vs. 47.8%)

Fertil Steril. 2019 Mar 25. pii: S0015-0282(19)30064-0. doi: 10.1016/j.fertnstert.2019.01.026. [Epub ahead of print]

Higher chromosomal aberration rate in miscarried conceptus from polycystic ovary syndrome women undergoing assisted reproductive treatment.

Li Y1, Wang L1, Xu J1, Niu W1, Shi H1, Hu L1, Zhang Y1, Zhang M1, Bao X1, Zhang N1, Sun Y2.

Author information

Abstract

OBJECTIVE:

To assess the potential association between polycystic ovary syndrome (PCOS) and chromosomally aberrant miscarriage during treatment with assisted reproductive technology (ART).

DESIGN:

A retrospective, single-center study.

SETTING:

University-affiliated reproductive center.

PATIENT(S):

A total of 328 patients sent their first trimester miscarried chorionic villus for genetic examination after ART in our center from January 2013 to September 2016, of which 119 cases were women with PCOS and 209 were non-PCOS controls. No known definite miscarriage-related concomitants existed in any study subject.

INTERVENTION(S):

Single nucleotide polymorphism array analysis was performed on all collected samples.

MAIN OUTCOME MEASURE(S):

Frequency of aberrant karyotype of miscarried conceptus and the correlation between PCOS and chromosomally aberrant miscarriage.

RESULT(S):

A total of 173 (52.7% of 328) conceptuses were identified as chromosomally aberrant by single nucleotide polymorphism array. Chromosomal aberrations were more frequent in conceptuses from PCOS patients compared with controls (61.3% vs. 47.8%). Furthermore, both univariate and multivariable analysis identified PCOS as a risk factor for an embryo/fetus to be chromosomally abnormal, with odds ratios of 1.957 (95% confidence interval, 1.067-3.590) and 2.008 (95% confidence interval, 1.038-3.883), respectively.

CONCLUSION(S):

Women with PCOS were at an increased risk of miscarrying a chromosomally aberrant embryo/fetus compared with non-PCOS controls during ART. Mechanisms require further investigation. Preimplantation genetic screening might be an effective approach to decrease the risk of spontaneous miscarriage for women with PCOS.