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胞浆内单精子注射在非男性因素不孕且进行胚胎植入前遗传学检测非整倍体(PGT-A)的夫妇中并不优于常规体外受精。

Intracytoplasmic sperm injection is not superior to conventional IVF in couples with non-male factor infertility and preimplantation genetic testing for aneuploidies (PGT-A).

机构信息

IVIRMA Middle East Fertility Clinic, IVF laboratory, Abu Dhabi, United Arab Emirates.

Obstetrical Department, Women's University Hospital Tuebingen, Tuebingen, Germany.

出版信息

Hum Reprod. 2020 Feb 29;35(2):317-327. doi: 10.1093/humrep/deaa002.

Abstract

STUDY QUESTION

Does the insemination method impact the euploidy outcome in couples with non-male factor infertility?

SUMMARY ANSWER

Conventional IVF can be applied in cycles with preimplantation genetic testing for aneuploidies (PGT-A), as both IVF and ICSI generate equal numbers of euploid blastocysts.

WHAT IS KNOWN ALREADY

Ever since its introduction, the popularity of ICSI has increased tremendously, even in couples with non-male factor infertility. The use of conventional IVF is a contraindication for couples undergoing PGT to ensure monospermic fertilisation and to eliminate potential paternal contamination from extraneous sperm attached to the zona pellucida. Despite this, it has recently been shown that sperm DNA fails to amplify under the conditions used for trophectoderm biopsy samples.

STUDY DESIGN, SIZE, DURATION: This single-centre prospective pilot study included 30 couples between November 2018 and April 2019.

PARTICIPANTS/MATERIALS, SETTING, METHOD: Arab couples, with a female age between 18-40 years, body mass index ≤30 kg/m2, at least 10 cumulus oocyte complexes (COCs) following oocyte retrieval (OR) and normal semen concentration and motility (WHO) in the fresh ejaculate on the day of OR, were eligible for the study. Half of the sibling oocytes were assigned to conventional IVF, and the other half were assigned to ICSI. All embryos were cultured in a time-lapse imaging system in Global Total LP media. Blastocysts were subjected to trophectoderm biopsy on Day 5, 6 or 7 and next-generation sequencing (NGS) to determine blastocyst ploidy status. The primary objective was to determine the euploid rate in blastocysts from sibling oocytes.

MAIN RESULTS AND THE ROLE OF CHANCE

A total of 568 COCs were randomly allocated between IVF (n = 283; 9.4 ± 4.0) and ICSI (n = 285; 9.5 ± 4.1). While the incidence of normal fertilisation per cycle (6.1 ± 3.8 (64.0%) vs 6.3 ± 3.5 (65.4%); P = 0.609) was distributed equally between IVF and ICSI, the degeneration rate (0.1 ± 0.3 vs 0.7 ± 0.8; P = 0.0003) was significantly higher after ICSI and the incidence of abnormal fertilisation (≥3 pronuclei) was significantly higher after IVF (0.9 ± 1.2 vs 0.2 ± 0.4; P = 0.005). For all fertilised oocytes, there were no differences in the number of good-quality embryos on Day 3 (74% vs 78%; P = 0.467), nor in the blastulation rate on Day 5 (80.4% vs 70.8%; P = 0.076). The total number of blastocysts biopsied per cycle on Days 5, 6 and 7 was not significantly different between IVF or ICSI (4.0 ± 2.8 vs 3.9 ± 2.5; P = 0.774). With euploid rates of 49.8 and 44.1% (P = 0.755; OR: 1.05664 [0.75188-1.48494), respectively, there was no significant difference identified between IVF and ICSI (2.0 ± 1.8 vs 1.9 ± 1.7; P = 0.808) and all couples had at least one euploid blastocyst available for transfer. When considering only euploid blastocysts, the male/female ratio was 61/39 in IVF and 43/57 in ICSI (P = 0.063).

LIMITATIONS, REASON FOR CAUTION: This is a pilot study with a limited patient population of 30 couples (and 568 COCs) with a normal ovarian response. The results of our study should not be extrapolated to other patient populations.

WIDER IMPLICATIONS OF THE FINDINGS

It is safe to apply conventional IVF in couples with non-male factor infertility undergoing PGT-A.

STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained. There are no competing interests.

TRIAL REGISTRATION NUMBER

NCT03708991.

摘要

研究问题

非男性因素不孕患者的授精方法是否会影响胚胎的整倍体结果?

总结答案

传统的体外受精(IVF)可应用于植入前遗传学检测整倍体(PGT-A)的周期中,因为 IVF 和卵胞浆内单精子注射(ICSI)都会产生相同数量的整倍体囊胚。

已知情况

自引入以来,ICSI 的普及程度大大增加,即使在非男性因素不孕的夫妇中也是如此。使用传统的 IVF 是进行 PGT 的禁忌症,以确保单精子受精并消除潜在的来自与透明带附着的外来精子的父系污染。尽管如此,最近已经表明,在用于滋养外胚层活检样本的条件下,精子 DNA 无法扩增。

研究设计、规模、持续时间:这是一项单中心前瞻性试点研究,纳入了 2018 年 11 月至 2019 年 4 月期间的 30 对夫妇。

参与者/材料、地点、方法:符合研究条件的阿拉伯夫妇,女性年龄在 18-40 岁之间,体重指数(BMI)≤30kg/m2,取卵(OR)后至少有 10 个卵丘卵母细胞复合物(COCs),并且新鲜精液中的精子浓度和活力(WHO)正常。将一半的同卵 COCs 分配给常规 IVF,另一半分配给 ICSI。所有胚胎均在 Global Total LP 培养基中进行时间延迟成像系统培养。囊胚于第 5、6 或 7 天进行滋养外胚层活检,并进行下一代测序(NGS)以确定囊胚的整倍体状态。主要目的是确定同卵 COCs 囊胚的整倍体率。

主要结果和机会作用

总共随机分配了 568 个 COCs 进行 IVF(n=283;9.4±4.0)和 ICSI(n=285;9.5±4.1)。虽然每个周期的正常受精发生率(6.1±3.8(64.0%)与 6.3±3.5(65.4%);P=0.609)在 IVF 和 ICSI 之间相等,但 ICSI 后的退化率(0.1±0.3 与 0.7±0.8;P=0.0003)显著更高,IVF 后异常受精(≥3 个原核)的发生率(0.9±1.2 与 0.2±0.4;P=0.005)显著更高。对于所有受精的卵子,第 3 天的优质胚胎数量(74% 与 78%;P=0.467)或第 5 天的囊胚形成率(80.4% 与 70.8%;P=0.076)均无差异。第 5、6 和 7 天每个周期活检的囊胚总数在 IVF 或 ICSI 之间没有显著差异(4.0±2.8 与 3.9±2.5;P=0.774)。IVF 和 ICSI 的整倍体率分别为 49.8%和 44.1%(P=0.755;OR:1.05664[0.75188-1.48494]),无显著差异(2.0±1.8 与 1.9±1.7;P=0.808),所有夫妇均至少有一个可用的整倍体囊胚进行转移。当仅考虑整倍体囊胚时,IVF 中的男性/女性比例为 61/39,而 ICSI 中为 43/57(P=0.063)。

局限性、谨慎的原因:这是一项试点研究,仅纳入了 30 对(568 个 COCs)卵巢反应正常的夫妇。我们的研究结果不应推广到其他患者群体。

研究结果的意义

在进行 PGT-A 的非男性因素不孕患者中,应用常规 IVF 是安全的。

研究资金/利益冲突:未获得资金。没有利益冲突。

试验注册编号

NCT03708991。

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