子宮內膜異位瘤之病患  以基礎濾泡(antral follicle count)比AMH更有效於評估卵巢功能
子宮內膜異位瘤之病患 vs 正常卵巢病患，縱使AMH數值相同 ，子宮內膜異位瘤病患之卵子數目仍顯較少

J Obstet Gynaecol. 2019 May;39(4):516-521. doi: 10.1080/01443615.2018.1533542. Epub 2019 Feb 11.

Does the anti-Müllerian hormone truly reflect ovarian response in women with endometrioma?

Inal ZO1, Engin Ustun Y2, Yilmaz N2, Aktulay A2, Bardakci Y3, Gulerman C2.

Abstract

In this study, our aim was to determine which factor is more correlated with the number of oocytes retrieved in patients with endometrioma compared with controls undergoing in vitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI) cycles: antral follicle count (AFC) or anti-Müllerian hormone (AMH). A total of 60 women with endometrioma and a control population of 60 women without endometrioma in the same period were randomly selected underwent the injection IVF-ICSI treatment. No significant differences were found between the groups in terms of age (28.78 ± 3.49 vs. 29.52 ± 2.47, p = .187), body mass index (23.62 ± 2.05 vs. 23.91 ± 2.11, p = .449), duration of infertility [(3 (2-4) vs. 3 (2-3), p = .139)], AMH level (1.52 ± 0.51 vs. 1.32 ± 0.92, p = .133), duration of stimulation [(9 (9-10) vs. 10 (9-10), p = .135)], total gonadotropin dose [(2750 (2262.5-3337.5) vs. 2770 (2680-3562.5), p = .125)], endometrial thickness [(10 (10-11) vs. 10 (9-11), p = .463)], fertilisation rates (67.20 ± 18.04 vs. 62.28 ± 17.13, p = .123), grade I embryo (43.3% vs. 30%, p = .185), clinical pregnancy rates (40% vs. 26.7%, p = .123), and the perinatal outcomes between the groups. The AFC was higher in the controls than in those with endometrioma (9.20 ± 1.80 vs. 6.32 ± 2.04, p < .001). The number of oocytes retrieved was also higher in the controls than in those with endometrioma [(7 (6-8) vs. 4 (4-5.75), p < .001)]. We found that women with endometrioma had a significantly lower number of oocytes retrieved than the controls despite the same AMH levels in both groups. AFC is a better marker of ovarian response than AMH in women with endometrioma undergoing IVF-ICSI. Impact statement What is already known on this subject? Utilising the ovarian reserve is important in the success of ovarian stimulation and in evaluating the success of assisted reproductive technologies. The anti-Müllerian hormone (AMH) level and the antral follicle count (AFC) are widely used in the prediction of ovarian functional reserve and response. However, no perfect marker exists in the evaluation of ovarian reserve and ovarian response. What do the results of this study add? Our study demonstrated that women with endometrioma have a significantly lower number of oocytes retrieved than the controls, despite the same AMH levels in both groups; which strongly suggests that AFC is a better reflection of ovarian response than AMH in women with endometrioma undergoing an in vitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI). What are the implications of these findings for clinical practice and/or further research? This important issue has been reviewed and discussed for years, however, the conclusions are still controversial. Additional research is needed to understand which ovarian reserve test could better predict ovarian response outcome?

精蟲與20%濾泡液共同培養可提升精蟲活動力&下降精蟲DNA異常率

J Assist Reprod Genet. 2019 Dec 5. doi: 10.1007/s10815-019-01643-2. [Epub ahead of print]

Co-incubation of spermatozoa with human follicular fluid reduces sperm DNA fragmentation by mitigating DNase activity in the seminal plasma.

Dorado-Silva M1, Bartolomé-Nebreda J2, Sánchez-Martín P1, Johnston S3, Gosálvez J2.

Author information

1

Ginemed, Clinic for Assisted Reproduction, Sevilla, Spain.

2

Unit of Genetics, Department of Biology, Universidad Autónoma de Madrid, Madrid, Spain.

3

School of Agriculture and Food Sciences, University of Queensland, Gatton, Australia. s.johnston1@uq.edu.au.

Abstract

PURPOSE:

To examine the effect of co-incubating spermatozoa with human follicular fluid (HFF) on the rate of sperm DNA fragmentation.

METHODS:

This prospective study used semen (n = 23) and HFF from oocyte donors (n = 23). Liquified semen was divided into four aliquots: (1) neat semen (NEAT), (2) seminal plasma removed and replaced with sperm media (HTF) containing 0% (FF0), (3) 20% (FF20), or (4) 50% (FF50) HFF. Sperm motility and DNA fragmentation (SDF) were assessed following 24 h of incubation at 37 °C. Pro-oxidant capacity of HFF and seminal plasma and the effect of HFF on seminal plasma DNase activity was assessed in a sub-sample of 10 ejaculates.

RESULTS:

Sperm motility was higher after 3 h of incubation in media that contained HFF compared to the NEAT sample or when sperm was diluted in media without HFF. r-SDF (increase of SDF per time unit) values after 24 h of incubation for NEAT, FF0, FF20 and FF50 were 0.91, 0.69, 0.25 and 0.36, respectively. While pro-oxidant capacity of seminal plasma samples showed large variation (mean: 94.6 colour units; SD 65.4), it was lower and more homogeneous in FF samples (mean: 29.9 colour units; SD: 6.3). Addition of HFF to seminal plasma appeared to inhibit DNase activity.

CONCLUSION:

While differences exist in the pro-oxidant capacity of seminal plasma of patients, sperm DNA integrity was preserved with addition of HFF to sperm media, irrespective of the level of pro-oxidant capacity. DNase activity in the original seminal plasma was abolished after HFF co-incubation.

肥胖PCO病患施行IVF容易流產
BMI應該控制在BMI < 25 kg/m2

Fertil Steril. 2019 Dec;112(6):1172-1179. doi: 10.1016/j.fertnstert.2019.08.009.

Effect of body mass index on pregnancy outcomes with the freeze-all strategy in women with polycystic ovarian syndrome.

Qiu M1, Tao Y1, Kuang Y2, Wang Y3.

Author information

Abstract

OBJECTIVE:

To investigate the effects of body mass index (BMI) on assisted reproductive outcomes with the freeze-all strategy for patients with polycystic ovary syndrome (PCOS).

DESIGN:

Retrospective cohort study.

SETTING:

Tertiary care academic medical center.

PATIENT(S):

A total of 3,079 women with PCOS across different BMIs at our institution from January 2015 to May 2017 were stratified into cohorts.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Implantation rate, clinical pregnancy rate, early miscarriage rate, and live birth rate.

RESULT(S):

The live birth rate was most favorable in underweight (BMI < 18.5 kg/m2) and normal weight cohorts (18.5 ≤ BMI < 25 kg/m2) and progressively decreased as BMI increased. Moreover, the obese cohort (BMI ≥ 30 kg/m2) of patients with PCOS who had frozen ET cycles had a relatively high early miscarriage rate.

CONCLUSION(S):

The live birth rates are highest in underweight and normal weight patients with PCOS undergoing IVF with the freeze-all strategy. Furthermore, there is a progressive and statistically significant decrease in the live birth rate and an increase in the miscarriage rate in obese patients with PCOS.

子宮內膜異位瘤平均會少25%卵子

Arch Gynecol Obstet. 2019 Dec;300(6):1759-1765. doi: 10.1007/s00404-019-05337-z. Epub 2019 Oct 30.

Endometriosis reduces ovarian response in controlled ovarian hyperstimulation independent of AMH, AFC, and women's age measured by follicular output rate (FORT) and number of oocytes retrieved.

Nicolaus K1, Bräuer D1, Sczesny R1, Jimenez-Cruz J1,2, Bühler K1, Hoppe I1, Runnebaum IB3.

Abstract

PURPOSE:

To determine the influence of endometriosis on the ovarian response during controlled ovarian hyperstimulation measured by number of oocytes retrieved and the follicular output rate (FORT).

METHODS:

A retrospective, single center study included 96 women, who underwent ICSI treatments for male factor infertility according to World Health Organisation between 2016 until 2018. A total of 96 patients were included in the study with 205 fresh ICSI cycles. The study group included 26 patients with endometriosis after surgical and medical treatment; the control group included 70 patients without endometriosis. The women with endometriosis underwent 47 and the control group 158 ICSI cycles. Women underwent fresh intracytoplasmatic sperm injection cycles after controlled ovarian hyperstimulation following a GnRH-antagonist protocol. The FORT was calculated as the ratio of pre-ovulatory follicle count × 100/small antral follicle count at baseline.

RESULTS:

A lower number of retrieved oocytes (5.89 vs. 7.25, p = 0.045), lower FORT (75.67 vs. 94.63, p = 0.046), lower number of metaphase II oocytes (4.87 vs. 6.04, p = 0.046), and lower fertilization rate after intracytoplasmatic sperm injection (40.61 vs. 57.76, p = 0.003) were found in women with endometriosis compared to women without endometriosis. The number of oocyctes retrieved was 0.71 lower in the group with endometriosis than in the group without (p = 0.026). The FORT was 24.55% lower in the group with endometriosis (p = 0.025).

CONCLUSIONS:

Endometriosis reduces the FORT and the number of metaphase-II oocytes after controlled ovarian hyperstimulation independly of women's age, antral follicle count and anti-Müllerian hormone.

黃體素過高易造成子宮內膜增強DNA methylation (DNMT1 and DNMT3B) & 降低adhesion molecule (MUC1, CDH1 and CTNNB1)

J Assist Reprod Genet. 2019 Nov 22. doi: 10.1007/s10815-019-01623-6. [Epub ahead of print]

Effects of high progesterone in in-vitro fertilization cycle on DNA methylation and gene expression of adhesion molecules on endometrium during implantation window.

Xiong Y1,2,3, Hu L1, Zhang T3, Wang M4, Xu H3, Li TC3, Sun Y5, Wang CC6,7,8.

Author information

Abstract

PURPOSE:

High progesterone is associated with low implantation rate. Our previous study demonstrated that DNA methylation in endometrium was increased in women with high progesterone in IVF cycles. However, the DNA methylation status is still not yet confirmed, and how it affects endometrial receptivity in high progesterone is still unknown. Current study investigated the effects of high progesterone on DNA methylation and gene expression of adhesion molecules on endometrium during implantation window.

METHODS:

A cohort study included 20 women with high progesterone (HP) and 20 with normal progesterone (NP) on the day of human chorionic gonadotropin (hCG) administration after controlled ovarian hyperstimulation in IVF cycle. Endometrial tissues were collected on the 7th day after hCG administration. Immunohistochemical staining of DNA methyltransferases (DNMT1 and DNMT3B) and adhesion molecules (MUC1, CDH1 and CTNNB1) were performed. Methylation of MUC1, CDH1, and CTNNB1 promoter regions was detected by Sequenom MassARRAY or bisulfite sequencing PCR. RT-qPCR was used to quantify mRNA expression levels, and correlation of methylation and gene expression level of the adhesion molecules were determined.

RESULTS:

DNMT3B, but not DNMT1, in nucleus of luminal and glandular epithelial cells in HP group was significantly higher than that in NP group. Promoter regions of CDH1 and CTNNB1, but not MUC1, in endometrium of HP group were hypermethylated. Protein and mRNA expression of MUC1, CDH1, and CTNNB1 in endometrium of HP group was significantly lower than that in NP group. Level of DNA methylation was negatively correlated with the gene expression of CDH1 and CTNNB1, but not MUC1.

CONCLUSIONS:

DNA hypermethylation and low expression of adhesion molecules on endometrium were associated with high progesterone during implantation window, which may contribute to the underlying epigenetic mechanism in the failure of IVF treatment.

KEYWORDS:

Adhesion molecules; DNA methylation; Endometrium; In vitro fertilization; Progesterone

不明原因之不孕症病患  研究顯示: 先生高齡對於IVF活產率有不良影響

Hum Reprod. 2019 Nov 26. pii: dez223. doi: 10.1093/humrep/dez223. [Epub ahead of print]

Male ageing is negatively associated with the chance of live birth in IVF/ICSI cycles for idiopathic infertility.

Horta F1, Vollenhoven B2,3,4, Healey M4,5, Busija L6, Catt S1, Temple-Smith P1.

Author information

1

EPRD, Department of Obstetrics and Gynecology, Monash University, Melbourne, VIC 3168, Australia.

2

Monash IVF, Melbourne, VIC 3168, Australia.

3

Monash Health, Melbourne, VIC 3169, Australia.

4

Department of Obstetrics and Gynecology, Monash University, Melbourne, VIC 3168, Australia.

5

Royal Women's Hospital, Melbourne, VIC 3052, Australia.

6

School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia.

Abstract

STUDY QUESTION:

Is male age associated with the clinical outcomes of IVF/ICSI cycles for idiopathic infertility after adjustment for female age?

SUMMARY ANSWER:

Male ageing is negatively associated with clinical IVF/ICSI outcomes in couples with idiopathic infertility independent of female age.

WHAT IS KNOWN ALREADY:

The effect of male age on the outcomes of infertility treatments is controversial and poorly explored. In contrast, fertility is known to decline significantly with female age beyond the mid-30s, and reduced oocyte quality plays an important role. The negative effect of male age on sperm quality is largely associated with an increasing susceptibility to sperm DNA damage. Although increasing maternal age has been linked with poorer oocyte quality, studies on the effect of male age have disregarded the need to control for female age making it difficult to define clearly the role of male age in infertile couples.

STUDY DESIGN, SIZE, DURATION:

This retrospective cohort study analysed 2425 cycles of couples with idiopathic infertility selected from a total of 24 411 IVF/ICSI cycles performed at Monash IVF in Australia between 1992 and 2017. The primary outcome was live birth and secondary outcomes were clinical pregnancy and miscarriage.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Couples with primary/secondary infertility who underwent IVF/ICSI cycles with male partners classified as normozoospermic were selected (inclusion criteria). Couples in which the female partner had endometriosis, tubal factors, polycystic ovarian syndrome, ovarian hyperstimulation syndrome, poor responders (≤3 mature oocytes retrieved) and couples with more than 15 cumulus oocyte complexes retrieved or who used cryopreserved gametes were excluded. Binary logistic multilevel modelling was used to identify the effect of male age and female age on clinical outcomes after controlling for confounding factors. Male age and female age were examined as continuous and categorical (male age: <40, 40-44, 45-49, 50-54, ≥55; female age:<30, 30-34, 35-39, ≥40) predictors.

MAIN RESULTS AND THE ROLE OF CHANCE:

There was a negative effect of male age and female age on live birth as odds ratios (OR) with 95% CI for each additional year of age (OR-male age: 0.96 [0.94-0.98]; OR-female age: 0.90 [0.88-0.93] P < 0.001). Potential interactions with male age such as type of treatment (IVF/ICSI), embryo transfer day (Day 3/Day 5) and female age did not have significant associations with outcomes (P > 0.05). Secondary outcomes showed a significant reduction in the odds of clinical pregnancy (OR-male age: 0.97 [0.96-0.99]; OR-female age: 0.92 [0.89-0.94] P < 0.001) and an increase in the odds of miscarriage with older age: male age (OR: 1.05 [1.01-1.08]; P = 0.002); female age (OR: 1.11 [1.05-1.18]; P < 0.001). Worse outcomes were associated with more cycles (clinical pregnancy-OR: 0.96 [0.93-0.99] P = 0.03; live birth-OR: 0.96 [0.92-0.99] P = 0.023) while more inseminated oocytes were associated with better outcomes (clinical pregnancy-OR: 1.06 [1.03-1.06] P < 0.001; live birth-OR: 1.07 [1.04-1.11] P < 0.001). Analyses for age categories showed a gradual worsening of clinical outcomes with increasing male age, with a significantly worse live birth and clinical pregnancy outcomes in males aged older than 50 years compared to males younger than 40 years (P < 0.05).

無精症之病患精蟲進行減數分裂過程常常(27%)發生減數分裂中期(metaphase)中止
進一步造成無法形成原始精細胞spermatid

Fertil Steril. 2019 Nov 22. pii: S0015-0282(19)31992-2. doi: 10.1016/j.fertnstert.2019.08.004. [Epub ahead of print]

Meiotic arrest occurs most frequently at metaphase and is often incomplete in azoospermic men.

Enguita-Marruedo A1, Sleddens-Linkels E1, Ooms M1, de Geus V1, Wilke M2, Blom E2, Dohle GR3, Looijenga LHJ4, van Cappellen W5, Baart EB6, Baarends WM7.

Author information

Abstract

OBJECTIVE:

To establish which meiotic checkpoints are activated in males with severe spermatogenic impairment to improve phenotypic characterization of meiotic defects.

DESIGN:

Retrospective observational study.

SETTING:

University medical center research laboratory and andrology clinic.

PATIENT(S):

Forty-eight patients with confirmed spermatogenic impairment (Johnsen scores 3-6) and 15 controls (Johnsen score 10).

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Quantitative assessment of immunofluorescent analyses of specific markers to determine meiotic entry, chromosome pairing, progression of DNA double-strand break repair, crossover formation, formation of meiotic metaphases, metaphase arrest, and spermatid formation, resulting in a novel classification of human meiotic arrest types.

RESULT(S):

Complete metaphase arrest was observed most frequently (27%), and the patients with the highest frequency of apoptotic metaphases also displayed a reduction in crossover number. Incomplete metaphase arrest was observed in 17% of the patients. Only four patients (8%) displayed a failure to complete meiotic chromosome pairing leading to pachytene arrest. Two new types of meiotic arrest were defined: premetaphase and postmetaphase arrest (15% and 13%, respectively).

CONCLUSION(S):

Meiotic arrest in men occurs most frequently at meiotic metaphase. This arrest can be incomplete, resulting in low numbers of spermatids, and often occurs in association with reduced crossover frequency. The phenotyping approach described here provides mechanistic insights to help identify candidate infertility genes and to assess genotype-phenotype correlations in individual cases.

IVF vs ICSI   形成囊胚

染色體正常率 (28 vs 30%)

aneuploid (45 vs 43.%)

mosaicism (26 vs 21%)

無訊號 (4  vs 6%)

J Assist Reprod Genet. 2019 Jan;36(1):153-157. doi: 10.1007/s10815-018-1347-6. Epub 2018 Oct 25.

Minimizing mosaicism: assessing the impact of fertilization method on rate of mosaicism after next-generation sequencing (NGS) preimplantation genetic testing for aneuploidy (PGT-A).

Palmerola KL1,2, Vitez SF3, Amrane S4,3, Fischer CP5, Forman EJ4.

Author information

Abstract

PURPOSE:

Advances in preimplantation genetic testing (PGT) have led to practice changes in assisted reproductive technologies (ART), enabling fertility centers to transfer single embryos while maintaining excellent ongoing pregnancy rates, reducing miscarriage rates, and dramatically reducing ART-associated multiple pregnancies. The introduction of next-generation sequencing (NGS) allows PGT laboratories to assess for embryo mosaicism-although the true incidence and reproductive potential of predicted mosaic embryos are controversial. Due to concern for genetic contamination from other spermatozoa, most reference laboratories require use of intracytoplasmic sperm injection (ICSI) for single gene preimplantation genetic diagnosis (PGT-M). However, in PGT for aneuploidy (PGT-A), conventional insemination (IVF) is typically permissible. The purpose of this study was to evaluate rates of euploid, aneuploid, and mosaic in trophectoderm biopsy samples from embryos in IVF versus ICSI PGT-A cycles. Secondary aims were to assess sex ratio, and subtypes of aneuploidy and mosaicism in IVF versus ICSI PGT-A cycles.

METHODS:

We performed a retrospective review of women undergoing PGT-A at a single academic fertility center from July 1, 2015, to September 1, 2017. In all cycles, PGT-A was performed via trophectoderm biopsy on day 5 or 6 and analyzed using NGS at a single reference lab. We collected and compared patient demographics, fertility testing, cycle characteristics, and PGT-A outcomes between IVF and ICSI cycles.

RESULTS:

Three hundred two PGT-A cycles were included for analysis: 75 IVF and 227 ICSI cycles, resulting in 251 IVF and 724 ICSI biopsied blastocysts. Mean oocyte age of included cycles was 38.6 years (IVF) and 38.5 years (ICSI), p = 0.85. Baseline characteristics of IVF and ICSI PGT-A cycles were similar with the exception of semen parameters: IVF cycles had higher sperm concentration and total motility compared to ICSI cycles. PGT-A outcomes did not differ between IVF and ICSI cycles: euploid 27.9% (IVF) versus 30% (ICSI); aneuploid 45.4% (IVF) versus 43.1% (ICSI); no result 4.4% (IVF) versus 6.2% (ICSI). Though not significant, we identified a trend toward higher rate of mosaicism in IVF (25.9%) versus ICSI (20.9%). Among mosaic embryos, a lower percentage of simple mosaic embryos resulted from IVF (53.8%) versus ICSI (70.2%). Among aneuploid embryos, a non-significant higher percentage of complex aneuploidy resulted from IVF (16.3%) versus ICSI (9%). IVF resulted in a non-significant higher proportion of cycles with no transferrable embryos (42.7%) versus ICSI (36.6%). Numerical and sex chromosome involvement in mosaicism and aneuploidy were similar between IVF and ICSI cycles.

CONCLUSION:

IVF and ICSI NGS PGT-A have similar rates of euploid, aneuploid, and no result embryos, though IVF may result in higher rates of mosaicism and demonstrates differences in proportions of mosaic and aneuploid subtypes compared to ICSI. ICSI may be preferable to conventional insemination to minimize the rate of mosaic results in NGS PGT-A cycles.

ICSI 精蟲品質很差  (vs ICSI 精蟲略差)造成
卵子受孕率下降3%
受孕後囊胚形成率下降1%
囊胚植入懷孕率無明顯差異

Fertil Steril. 2017 Dec;108(6):961-972.e3. doi: 10.1016/j.fertnstert.2017.08.033. Epub 2017 Oct 3.

Effect of the male factor on the clinical outcome of intracytoplasmic sperm injection combined with preimplantation aneuploidy testing: observational longitudinal cohort study of 1,219 consecutive cycles.

Mazzilli R1, Cimadomo D2, Vaiarelli A3, Capalbo A4, Dovere L5, Alviggi E6, Dusi L7, Foresta C8, Lombardo F9, Lenzi A9, Tournaye H10, Alviggi C11, Rienzi L12, Ubaldi FM12.

Author information

Abstract

OBJECTIVE:

To evaluate the impact of the male factor on the outcomes of intracytoplasmic sperm injection (ICSI) cycles combined with preimplantation genetic testing for aneuploidies (PGT-A).

DESIGN:

Observational longitudinal cohort study.

SETTING:

Private in vitro fertilization (IVF) center.

PATIENT(S):

A total of 1,219 oocyte retrievals divided into five study groups according to sperm parameters: normozoospermia (N), moderate male factor (MMF), severe oligoasthenoteratozoospermia (OAT-S), obstructive azoospermia (OA), and nonobstructive azoospermia (NOA).

INTERVENTION(S):

ICSI with ejaculated/surgically retrieved sperm, blastocyst culture, trophectoderm-based quantitative polymerase chain reaction PGT-A, and frozen-warmed euploid embryo transfer (ET).

MAIN OUTCOMES MEASURE(S):

The primary outcome measures were fertilization, blastocyst development, and euploidy rates; the secondary outcome measures were live birth and miscarriage rates. Perinatal and obstetrical outcomes were monitored as well.

RESULT(S):

A total of 9,042 metaphase II oocytes were inseminated. The fertilization rate was significantly reduced in MMF, OAT-S, OA, and NOA compared with N (74.8%, 68.7%, 67.3%, and 53.1% vs. 77.2%). The blastocyst rate per fertilized oocyte was significantly reduced in MMF and NOA compared with N (48.6% and 40.6% vs. 49.3%). The timing of blastocyst development also was affected in OA and NOA. Logistic regression analysis adjusted for confounders highlighted NOA as a negative predictor of obtaining an euploid blastocyst per OPU (odds ratio 0.5). When the analysis was performed per obtained blastocyst, however, no correlation between male factor and euploidy rate was observed. Embryo transfers also resulted in similar live birth and miscarriage rates. No impact of sperm factor on obstetrical/perinatal outcomes was observed.

CONCLUSION(S):

Severe male factor impairs early embryonic competence in terms of fertilization rate and developmental potential. However, the euploidy rate and implantation potential of the obtained blastocysts are independent from sperm quality.

卵子之染色體或紡錘體正常與否可能是決定IVF成功與否之最重要關鍵

Fertil Steril. 2019 Nov 15. pii: S0015-0282(19)32276-9. doi: 10.1016/j.fertnstert.2019.08.070. [Epub ahead of print]

Oocyte meiotic spindle morphology is a predictive marker of blastocyst ploidy-a prospective cohort study.

Tilia L1, Chapman M2, Kilani S2, Cooke S2, Venetis C3.

Author information

Abstract

OBJECTIVE:

To evaluate oocyte meiotic spindle (OMS) morphology at intracytoplasmic sperm injection (ICSI) as a predictor of blastocyst ploidy and whether OMS morphology could aid standard morphology-based blastocyst selection.

DESIGN:

Prospective cohort study.

SETTING:

In vitro fertilization clinic.

PATIENT(S):

Patients undergoing ICSI cycles with an intention to perform preimplantation genetic testing for aneuploidy (PGT-A) from October 2014 to December 2017.

INTERVENTION(S):

The OMS was visualized with the use of polarized light microscopy at the time of ICSI and the morphology classified as normal, dysmorphic, translucent, not visible, or in telophase. Blastocyst biopsy for PGT-A was performed on embryos with suitable development.

MAIN OUTCOME MEASURE(S):

The association of OMS morphology with the resulting blastocyst ploidy was evaluated on an "intention-to-treat" (ITT) and an "as-treated analysis" (ATA) basis.

RESULT(S):

The morphology of 2,056 OMSs were classified. A strong association of OMS morphology with fertilization, cleavage to at least 6 cells on day 3, and good/top-quality blastocyst formation was present. Normal OMS was positively associated with blastocyst euploidy compared with all other OMS types combined, per either ITT or ATA. Even after controlling for female age, blastocyst quality, and developmental stage, the presence of a normal OMS was strongly associated with the probability of blastocyst euploidy.

CONCLUSION(S):

OMS morphology is a predictive marker of blastocyst ploidy and can potentially aid standard morphology-based blastocyst selection.

傳統以為PCO病患服用pill可提高試管懷孕率
本篇指出服用pill反而降低試管活產率  尤其是使用GnRH antagonist療程之病患

Arch Gynecol Obstet. 2019 Sep;300(3):737-750. doi: 10.1007/s00404-019-05210-z. Epub 2019 Jun 6.

Effect of pretreatment with combined oral contraceptives on outcomes of assisted reproductive technology for women with polycystic ovary syndrome: a meta-analysis.

OBJECTIVE:

To evaluate the effect of pretreatment with combined oral contraceptives (COC) on outcomes in women with polycystic ovary syndrome (PCOS) who underwent assisted reproductive technology for subfertility.

METHODS:

Two authors independently searched MEDLINE, EMBASE, and the Cochran Library to identify and review articles published from October 1995 until December 2018 according to selection criteria. Outcomes are expressed as mean difference and odds ratio (OR) in a meta-analysis model.

RESULTS:

A total of seven studies were included in this meta-analysis: one randomized controlled study and two prospective and four retrospective cohort studies. Meta-analysis showed that the COC pretreatment did not affect rate of clinical pregnancy (OR = 0.93, 95% confidence interval CI 0.65-1.34, I2 = 76%) or ovarian hyperstimulation syndrome (OR = 0.90, 95% CI 0.57-1.44, I2 = 0%). However, the rate of miscarriage in the COC group was significantly higher (OR = 1.33, 95% CI 1.02-1.72, I2 = 9%) and the rate of cumulative live birth was significantly lower compared with the control group (OR = 0.72, 95% CI 0.54-0.98, I2 = 55%). Subgroup analysis showed higher rates of miscarriage and lower rates of cumulative live birth in studies with a gonadotropin-releasing hormone (GnRH) antagonist protocol (OR = 1.69, 95% CI 1.17-2.44, I2 = 0% and OR = 0.38, 95% CI 0.29-0.50, respectively).

CONCLUSION:

Pretreatment with COC in women with PCOS before assisted reproductive technology may have an adverse effect on clinical outcomes, especially with a GnRH antagonist protocol.

Day 5形成的囊胚67.7%染色體是正常  著床率: 68.9%
Day  6形成的囊胚52.1%染色體是正常  著床率: 66.8%
Day  7形成的囊胚43.1%染色體是正常  著床率: 52.6%

Hum Reprod. 2019 Sep 29;34(9):1632-1639. doi: 10.1093/humrep/dez138.

Worth the wait? Day 7 blastocysts have lower euploidy rates but similar sustained implantation rates as Day 5 and Day 6 blastocysts.

Abstract

STUDY QUESTION:

Does the reproductive potential of embryos change when blastocyst development takes longer than the traditionally accepted 5 days when accounting for aneuploidy and endometrial-embryo asynchrony?

SUMMARY ANSWER:

Aneuploidy increases with increasing duration of blastulation, but if blastocyst morphologic quality and endometrial-embryo asynchrony are controlled for, euploid Day 7 embryos have similar sustained implantation as compared to Days 5 and 6 euploid blastocysts.

WHAT IS KNOWN ALREADY:

The relative contributions of diminished embryo quality versus endometrial and embryo asynchrony to poor outcomes associated with embryos cultured past Day 6 are not clear. Asynchrony can be eliminated by embryo vitrification with transfer in a subsequent month after retrieval.

STUDY DESIGN, SIZE, DURATION:

Retrospective cohort study of patients from a single center attempting conception through ICSI and utilizing preimplantation genetic testing for aneuploidy screening (PGT-A) from January 2017 to September 2018. Cycles were excluded if they utilized surgical sperm or preimplantation genetic testing for monogenetic/single gene defects. ICSI cycle outcomes from 2586 patients were evaluated for ploidy status of embryos.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Only patients undergoing single, euploid frozen embryo transfer were included when analyzing cycle outcomes by day of blastocyst expansion of the transferred embryo (n = 2130). Ploidy rates by the day upon which an embryo was considered to be usable (denoted, 'usable blastulation day') were determined so as to assess the contribution of aneuploidy to slow embryo development. Outcomes of euploid frozen single embryo transfers (SET) of Day 7 embryos were evaluated to assess the reproductive potential associated with embryos that were slowly developing for reasons other than aneuploidy. Analyses were adjusted by maternal age and blastocyst morphology.

MAIN RESULTS AND THE ROLE OF CHANCE:

Overall, 67.7% (n = 3508) of usable Day 5 blastocysts were euploid, 52.1% (n = 5560) of usable Day 6 blastocysts were euploid and 43.1% (n = 229) of usable Day 7 embryos were euploid (Day 5 versus Day 6: odds ratio (OR) 0.7 (95% CI, 0.64-0.76), P < 0.001; Day 5 versus Day 7: OR 0.56 (95% CI, 0.46-0.69), P < 0.001; Day 6 versus Day 7: OR 0.81 (95% CI, 0.67-0.99), P = 0.036). Stratified by Society for Assisted Reproductive Technology maternal age groups, a reduction in the prevalence of euploidy by increasing time to embryo blastulation was still seen. The sustained implantation rate (SIR) was similar after euploid SET of Days 5 and 6 embryos (overall, 68.9% (95% CI, 66.0-71.6) and 66.8% (95% CI, 63.8-69.7), respectively; P = 0.81). SIR after euploid Day 7 SET appeared slightly lower than that of Days 5 and 6 embryos (52.6% (95% CI, 35.8-69.0); (Day 5 versus Day 7: OR, 0.67 (95% CI, 0.32-1.41), P = 0.29; Day 6 versus Day 7: OR 0.58 (95% CI, 0.28-1.2), P = 0.14)) but did not achieve statistical significance.

子宮內注射HCG無法明顯提高IVF-ET胚胎著床懷孕率

Arch Gynecol Obstet. 2018 Dec;298(6):1061-1069. doi: 10.1007/s00404-018-4923-1. Epub 2018 Oct 5.

Effect of intrauterine injection of human chorionic gonadotropin before fresh embryo transfer on IVF and ICSI outcomes: a meta-analysis.

Hou W1, Shi G1, Cai B1, Ding C1, Song J1, Zhang X1, Xu Y2.

Author information

1

Reproductive Medical Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

2

Reproductive Medical Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. xuyanwen663000@126.com.

Abstract

PURPOSE:

This analysis was performed to evaluate the effects of intrauterine injection of human chorionic gonadotropin (hCG) before fresh embryo transfer (ET) on the outcomes of in vitro fertilization and intracytoplasmic sperm injection.

METHODS:

Randomized controlled trials (RCTs) were identified by searching electronic databases. The outcomes of live birth, clinical pregnancy, implantation, biochemical pregnancy, ongoing pregnancy, ectopic pregnancy, and miscarriage between groups with and without hCG injections were analyzed. Summary measures were reported as risk ratios (RR) with 95% confidence intervals.

RESULTS:

Six RCTs on fresh embryo transfer (ET) were included in the meta-analysis. A total of 2759 women undergoing fresh ET were enrolled (hCG group n = 1429; control group n = 1330). Intrauterine injection of hCG significantly increased rates of biochemical pregnancy (RR 1.61) and ongoing pregnancy (RR 1.58) compared to controls. However, there were no significant differences in clinical pregnancy (RR 1.11), implantation (RR 1.17), miscarriage (RR 0.91), ectopic (RR 1.65) or live birth rates (RR 1.13) between the hCG group and control group.

CONCLUSION:

The current evidence for intrauterine injection of hCG before fresh ET does not support its use in an assisted reproduction cycle.