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.

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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.

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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.

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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.

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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.

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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.

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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).

IVF雙胞胎若其中一胎死腹中，存活胎兒較易早產及體重較輕

Hum Reprod. 2017 Nov 1;32(11):2298-2304. doi: 10.1093/humrep/dex277.

Vanishing twin syndrome among ART singletons and pregnancy outcomes.

Magnus MC1,2,3, Ghaderi S1, Morken NH4,5, Magnus P6,7, Bente Romundstad L8,9, Skjærven R4,10, Wilcox AJ11, Eldevik Håberg S6.

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Abstract

STUDY QUESTION:

Among babies born by ART, do singleton survivors of a vanishing twin have lower birth weight than other singletons?

SUMMARY ANSWER:

Vanishing twin syndrome (VTS) was associated with lower birth weight among ART singletons; a sibship analysis indicated that the association was not confounded by maternal characteristics that remain stable between deliveries.

WHAT IS KNOWN ALREADY:

Previous studies indicate that ART singletons with VTS have increased risk of adverse pregnancy outcomes, compared with other ART singletons. The potential contribution of unmeasured maternal background characteristics has been unclear.

STUDY DESIGN, SIZE AND DURATION:

This was a Norwegian population-based registry study, including 17 368 mothers with 20 410 ART singleton deliveries between January 1984 and December 2013.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The study population included 17 291 ART singletons without VTS, 638 ART singletons with VTS and 2418 ART singletons with uncertain vanishing twin status. We estimated differences in birth weight and gestational age comparing ART singletons with VTS first to all ART singletons without VTS, and subsequently to their ART siblings without VTS, using random- and fixed-effects linear regression, respectively. The corresponding comparisons for the associations with preterm birth and small for gestational age (SGA) were conducted using random-and fixed-effects logistic regression. The sibling analysis of preterm birth included 587 discordant siblings, while the sibling analysis of SGA included 674 discordant siblings.

MAIN RESULTS AND THE ROLE OF CHANCE:

ART singletons with VTS had lower birth weight when compared to all ART singletons without VTS, with an adjusted mean difference (95% CI) of -116 g (-165, -67). When we compared ART singletons with VTS to their ART singletons sibling without VTS, the adjusted mean difference was -112 g (-209, -15). ART singletons with VTS also had increased risk of being born SGA, with an adjusted odds ratio (OR) (95% CI) of 1.48 (1.07, 2.03) compared to all ART singletons without VTS, and 2.79 (1.12, 6.91) in the sibship analyses. ART singletons with VTS were also more likely to be born preterm, although this difference did not reach statistical significance.

排卵針劑量並不明顯影響囊胚期胚胎之染色體異常率
年齡明顯影響囊胚期胚胎之染色體異常率

Hum Reprod. 2017 Nov 1;32(11):2209-2217. doi: 10.1093/humrep/dex299.

High gonadotropin dosage does not affect euploidy and pregnancy rates in IVF PGS cycles with single embryo transfer.

Barash OO1, Hinckley MD1, Rosenbluth EM1, Ivani KA1, Weckstein LN1.

Author information

1

Reproductive Science Center of the San Francisco Bay Area, 100 Park Place, Suite 200, San Ramon, CA 94583, USA.

Abstract

STUDY QUESTION:

Does high gonadotropin dosage affect euploidy and pregnancy rates in PGS cycles with single embryo transfer?

SUMMARY ANSWER:

High gonadotropin dosage does NOT affect euploidy and pregnancy rates in PGS cycles with single embryo transfer.

WHAT IS KNOWN ALREADY:

PGS has been proven to be the most effective and reliable method for embryo selection in IVF cycles. Euploidy and blastulation rates decrease significantly with advancing maternal age. In order to recruit an adequate number of follicles, the average dosage of gonadotropins administered during controlled ovarian stimulation in IVF cycles often increases significantly with advancing maternal age.

STUDY DESIGN, SIZE, AND DURATION:

A retrospective study of SNP (Single Nucleotide Polymorphism) PGS outcome data from blastocysts biopsied on day 5 or day 6 was conducted to identify differences in euploidy and clinical pregnancy rates. Seven hundred and ninety four cycles of IVF treatment with PGS between January 2013 and January 2017 followed by 651 frozen embryo transfers were included in the study (506 patients, maternal age (y.o.) - 37.2 ± 4.31).

PARTICIPANTS/MATERIALS, SETTING, METHODS:

A total of 4034 embryos were analyzed (5.1 ± 3.76 per case) for euploidy status. All embryos were vitrified after biopsy, and selected embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. All cycles were analyzed by total gonadotropin dosage (<3000 IU, 3000-5000 IU and >5000 IU), by number of eggs retrieved (1-5, 5-10, 10-15 and >15 eggs) and patient's age (<35, 35-37, 38-40 and ≥41 y.o.). Clinical pregnancy rate was defined by the presence of a fetal heartbeat at 6-7 weeks of gestation.

MAIN RESULTS AND THE ROLE OF CHANCE:

Euploidy rates within the same age group were not statistically different regardless of the total dosage of gonadotropins used or the number of eggs retrieved. In the youngest group of patients (<35 y.o. - 187 IVF cycles) euploidy rates ranged from 62.3% (<3000 IU were used in the IVF cycle) to 67.5% (>5000 IU were used in the IVF cycle) (OR = 0.862, 95% CI 0.687-1.082, P = 0.2) and from 69.5% (1-5 eggs retrieved) to 60.0% (>15 eggs retrieved) (OR = 0.658, 95% CI 0.405-1.071, P = 0.09). Similar data were obtained in the oldest group of patients (≥41 y.o. - 189 IVF cycles): euploidy rates ranged from 30.7 to 26.4% (OR = 0.811, 95% CI 0.452-1.454, P = 0.481) when analyzed by total dosage of gonadotropins used in the IVF cycle and from 40.0 to 30.7% (OR = 0.531, 95% CI 0.204-1.384, P = 0.19), when assessed by the total number of eggs retrieved. Ongoing pregnancy rates were similar, not only within particular age groups, but also between different age groups regardless of the total dosage of gonadotropins used: ranging from to 63.6% (<3000 IU, < 35 y.o.) to 54.8% (>5000 IU, ≥41 y.o) (OR = 0.696, 95% CI 0.310-1.565, P = 0.38).

人工受精後不需要臥床休息15分鐘

Hum Reprod. 2017 Nov 1;32(11):2218-2224. doi: 10.1093/humrep/dex302.

Immobilization or mobilization after IUI: an RCT.

van Rijswijk J1, Caanen MR1, Mijatovic V1, Vergouw CG1, van de Ven PM2, Lambalk CB1, Schats R1.

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Abstract

STUDY QUESTION:

Does 15 min of immobilization after IUI improve pregnancy rates?

SUMMARY ANSWER:

Immobilization for 15 min after IUI does not improve pregnancy rates.

WHAT IS KNOWN ALREADY:

Prior RCTs report a beneficial effect of supine immobilization for 15 min following IUI compared to immediate mobilization, however, these studies can be criticized. Given the importance for the logistics in daily practice and the lack of biological plausibility we planned a replication study prior to potential implementation of this procedure.

STUDY DESIGN, SIZE, DURATION:

A single centre RCT, based in an academic setting in the Netherlands, was performed. Participants were randomly assigned for 15 min of supine immobilization following IUI for a maximum of six cycles compared to the standard procedure of immediate mobilization following IUI. Participants and caregivers were not blinded to group assignment. An independent researcher used computer-generated tables to allocate treatments. Stratification occurred to the indication of IUI (unexplained or mild male subfertility). Revelation of allocation took place just before the insemination by the caregiver. The primary outcome was ongoing pregnancy rate per couple.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

A total of 498 couples diagnosed with unexplained or mild male subfertility and an indication for treatment with IUI were approached and randomized in the study, of which 244 participants were assigned to 15 min of supine immobilization and 254 participants to immediate mobilization.

MAIN RESULTS AND THE ROLE OF CHANCE:

Participant characteristics were comparable between the groups, and 236 participants were analysed in the immobilization group, versus 245 in the mobilization group. The ongoing pregnancy rate per couple was not found to be superior in the immobilization group (one-sided P-value = 0.97) with 76/236 ongoing pregnancies (32.2%) being accomplished in the immobilization and 98/245 ongoing pregnancies (40.0%) in the immediate mobilization group (relative risk 0.81; 95% CI [0.63, 1.02], risk difference: -7.8%, 95% CI [-16.4%, 0.8%]). No difference was found in miscarriage rate, multiple gestation rate, live birth rate and time to pregnancy between the groups.

凍胚植入時, 若P4過低(<9 ng/ml)可能導致懷孕率明顯下降

Hum Reprod. 2017 Oct 13:1-6. doi: 10.1093/humrep/dex316. [Epub ahead of print]

Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study.

Labarta E1, Mariani G1, Holtmann N2,3, Celada P1, Remohí J1, Bosch E1.

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Abstract

STUDY QUESTION:

Is there a relationship between serum progesterone (P) and endometrial volume on the day of embryo transfer (ET) with ongoing pregnancy rate (OPR) in artificial endometrium preparation cycles?

SUMMARY ANSWER:

Patients with serum P < 9.2 ng/ml on the day of ET had a significantly lower OPR but endometrial volume was not related with OPR.

WHAT IS KNOWN ALREADY:

A window of optimal serum P levels during the embryo implantation period has been described in artificial endometrium preparation cycles. A very low endometrial volume is related to poor reproductive outcome.

STUDY DESIGN, SIZE, DURATION:

Prospective cohort study with 244 patients who underwent ET in an oocyte donation cycle after an artificial endometrial preparation cycle with estradiol valerate and vaginal micronized progesterone (400 mg/12 h). The study period went from 22 February 2016 to 25 October 2016 (8 months). Sample size was calculated to detect a 20% difference in OPR (35-55%) between two groups according to serum P levels in a two-sided test (80% statistical power, 95% confidence interval (CI)).

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Patients undergoing their first/second oocyte donation cycle, aged <50, BMI < 30 kg/m2, triple layer endometrium >6.5 mm and 1-2 good quality transferred blastocysts. A private infertility centre. Serum P determination and 3D ultrasound of uterine cavity were performed on the day of ET. Endometrial volume measurements were taken using a virtual organ computer-aided analysis (VOCAL™) system. The primary endpoint was OPR beyond pregnancy week 12.

MAIN RESULTS AND ROLE OF CHANCE:

About 211 of the 244 recruited patients fulfilled all the inclusion/exclusion criteria. Mean serum P on the day of embryo transfer was 12.7 ± 5.4 ng/ml (Centiles 25, 9.2; 50, 11.8; 75,15.8). OPRs according to serum P quartiles were: Q1: 32.7%; Q2: 49.1%; Q3: 58.5%; Q4: 50.9%. The OPR of Q1 was significantly lower than Q2-Q4: 32.7% versus 52.8%; P = 0.016; RR (95% CI): 0.62 (0.41-0.94). The mean endometrial volume was 3.4 ± 1.9 ml. Serum P on the day of ET did not correlate with endometrial volume. A logistic regression analysis, adjusted for all the potential confounders, showed that OPR significantly lowered between women with serum P < 9.2 ng/ml versus ≥9.2 ng/ml (OR: 0.297; 95%CI: 0.113-0.779); P = 0.013. The ROC curve showed a significant predictive value of serum P levels on the day of ET for OPR, with an AUC (95%CI) = 0.59 (0.51-0.67).

LIMITATIONS, REASONS FOR CAUTION:

Only the women with normal uterine cavity, appropriate endometrial thickness and good quality blastocysts transfer were included. Extrapolation to an unselected population or to other routes and/or doses of administering P needs to be validated. The role of endometrial volume could not be fully defined as very few patients presented a very low volume.

WIDER IMPLICATIONS OF THE FINDINGS:

The present study suggests a minimum threshold of serum P values on the day of ET that needs to be reached in artificial endometrial preparation cycles to optimize outcome. No upper threshold could be defined.

 胚胎染色體異常主要發生於受孕後之有絲分裂過程(D1-3)

Hum Reprod. 2017 Nov 8:1-12. doi: 10.1093/humrep/dex324. [Epub ahead of print]

The incidence and origin of segmental aneuploidy in human oocytes and preimplantation embryos.

Babariya D1,2, Fragouli E1,2, Alfarawati S1,2, Spath K1,2, Wells D1,2.

Author information

Abstract

STUDY QUESTION:

What is the incidence, origin and clinical significance of segmental aneuploidy in human oocytes and preimplantation embryos?

SUMMARY ANSWER:

Segmental aneuploidy occurs at a considerable frequency in preimplantation embryos with a majority being mitotic in origin.

WHAT IS KNOWN ALREADY:

In recent years, accurate techniques for the detection of aneuploidy in single cells have been developed. Research using such methods has confirmed that aneuploidy is a common feature of human oocytes and preimplantation embryos. However, thus far research has mainly focused on loss or gain of whole chromosomes. We utilized sensitive molecular methods to study another important form of cytogenetic abnormality at the earliest stages of human development, namely segmental aneuploidy.

STUDY DESIGN, SIZE, DURATION:

Chromosomal copy number data was obtained from oocytes and embryos of 635 IVF patients, who requested chromosome screening for various reasons, most commonly for advanced maternal age or previously unsuccessful IVF treatments. A total of 3541 samples comprising of 452 human oocytes, 1762 cleavage stage and 1327 blastocyst stage embryos were investigated in the present study.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Whole genome amplification (Sureplex, Illumina) was performed on cells biopsied from oocytes and embryos of IVF patients who requested chromosome screening. The samples were subsequently processed and analyzed for their chromosome complement using microarray comparative genomic hybridization (aCGH), (Illumina, Cambridge, UK).

MAIN RESULTS AND THE ROLE OF CHANCE:

Segmental abnormalities, involving loss or gain of chromosomal fragments in excess of 15 Mb, were found to occur at a high frequency. The incidence of such abnormalities was 10.4% in oocytes, but this increased dramatically during the first 3 days of embryonic development (24.3%), before starting to decline as embryos reached the final (blastocyst) stage of preimplantation development (15.6%). While some segmental errors were clearly of meiotic origin, most appear to arise during the first few mitoses following fertilization. The reduction in frequency at the blastocyst stage suggests that many cells/embryos affected by segmental abnormalities are eliminated (e.g. via arrest of the affected embryos or apoptosis of abnormal cells). Interestingly, sites of chromosome breakage associated with segmental aneuploidy were not entirely random but tended to occur within distinct chromosomal regions. Some of the identified hotspots correspond to known fragile sites while others may be considered novel and may be specific to gametogenesis and/or embryogenesis.